Mendrick, Donna (Gaithersburg, MD, US)
Porter, Mark (Gaithersburg, MD, US)
Johnson, Kory (Gaithersburg, MD, US)
Higgs, Brandon (Gaithersburg, MD, US)
Castle, Arthur (Gaithersburg, MD, US)
Elashoff, Michael (Gaithersburg, MD, US)

11/036196

09/16/2008

01/18/2005

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Ocimum Biosolutions, Inc. (Indianapolis, IN, US)

702/19

700/30, 435/6, 707/104.1, 702/22

G06F19/00

5811231	Methods and kits for eukaryotic gene profiling	September, 1998	Farr et al.
5858659	Polymorphism detection	January, 1999	Sapolsky et al.
5953727	Project-based full-length biomolecular sequence database	September, 1999	Maslyn et al.	707/104
5965352	Methods for identifying pathways of drug action	October, 1999	Stoughton et al.	435/4
6132969	Methods for testing biological network models	October, 2000	Stoughton et al.
6153421	Cloned genomes of infectious hepatitis C viruses and uses thereof	November, 2000	Yanagi et al.
6160105	Monitoring toxicological responses	December, 2000	Cunningham et al.	536/23.1
6185561	Method and apparatus for providing and expression data mining database	February, 2001	Balaban et al.	707/6
6203987	Methods for using co-regulated genesets to enhance detection and classification of gene expression patterns	March, 2001	Friend et al.
6218122	Methods of monitoring disease states and therapies using gene expression profiles	April, 2001	Friend et al.
6228589	Measurement of gene expression profiles in toxicity determination	May, 2001	Brenner
6229911	Method and apparatus for providing a bioinformatics database	May, 2001	Balaban et al.	382/128
6365352	Process to study changes in gene expression in granulocytic cells	April, 2002	Yerramilli et al.
6372431	Mammalian toxicological response markers	April, 2002	Cunningham et al.
6403778	Toxicological response markers	June, 2002	Cunningham et al.
6421612	System, method and computer program product for identifying chemical compounds having desired properties	July, 2002	Agrafiotis et al.
6461807	Methods for drug target screening	October, 2002	Friend et al.
20010039006	Toxicity typing using embryoid bodies	November, 2001	Snodgrass
20010049139	Hepatic regeneration from hematopoietic stem cells	December, 2001	Lagasse et al.
20020119462	Molecular toxicology modeling	August, 2002	Mendrick et al.
20020142284	Methods of identifying renal protective factors	October, 2002	Raha et al.
20030028327	Systems and methods for monitoring behavior informatics	February, 2003	Brunner et al.
20030124552	Biochips and method of screening using drug induced gene and protein expression profiling	July, 2003	Lindemann et al.
20030154032	Methods and compositions for diagnosing and treating rheumatoid arthritis	August, 2003	Pittman et al.

WO/1993/001205	January, 1993			TYROSINE KINASE
WO/1994/017208	April, 1994			METHODS AND DIAGNOSTIC KITS UTILIZING MAMMALIAN STRESS PROMOTERS TO DETERMINE TOXICITY OF A COMPOUND
WO/1995/011755	May, 1995			MICROFABRICATED, FLOWTHROUGH POROUS APPARATUS FOR DISCRETE DETECTION OF BINDING REACTIONS
WO/1997/013877	April, 1997			MEASUREMENT OF GENE EXPRESSION PROFILES IN TOXICITY DETERMINATION
WO/1997/016732	May, 1997			A PROCESS FOR IN VITRO ANALYSIS OF TOXIC AND ALLERGENIC SUBSTANCES
WO/1999/012118	March, 1999			COMPOUND SCREENING SYSTEM
WO/1999/027090	June, 1999			METHODS FOR IDENTIFYING THE TOXIC/PATHOLOGIC EFFECT OF ENVIRONMENTAL STIMULI ON GENE TRANSCRIPTION
WO/1999/032660	July, 1999			EXPLOITING GENOMICS IN THE SEARCH FOR NEW DRUGS
WO/1999/043345	September, 1999			AMINO ACID DEGRADING ENZYMES MODULATE CELL DEATH
WO/1999/058670	November, 1999			AGS PROTEINS AND NUCLEIC ACID MOLECULES AND USES THEREFOR
WO/2000/028092	May, 2000			METHOD FOR GENERATING GENE EXPRESSION PROFILES
WO/2000/039336	July, 2000			METHODS OF CHARACTERIZING DRUG ACTIVITIES USING CONSENSUS PROFILES
WO/2000/047761	August, 2000			HIGH-THROUGHPUT TOXICOLOGICAL TESTING USING CULTURED ORGANISMS AND CELLS
WO/2000/012760	September, 2000			TOXICOLOGICAL RESPONSE MARKERS
WO/2000/063435	October, 2000			METHOD OF IDENTIFYING TOXIC AGENTS USING DIFFERENTIAL GENE EXPRESSION
WO/2001/002609	January, 2001			METHOD OF IDENTIFYING TOXIC AGENTS USING DIFFERENTIAL GENE EXPRESSION
WO/2001/011076	February, 2001			IN VIVO HIGH THROUGHPUT TOXICOLOGY SCREENING METHOD
WO/2001/014425	March, 2001			MULTIPURPOSE DIAGNOSTIC SYSTEMS USING PROTEIN CHIPS
WO/2001/020043	March, 2001			METHOD OF CLUSTER ANALYSIS OF GENE EXPRESSION PROFILES
WO/2001/023886	April, 2001			IMPROVED TOXICITY SCREENING METHOD
WO/2001/025473	April, 2001			SYSTEMS AND METHODS FOR CHARACTERIZING A BIOLOGICAL CONDITION OR AGENT USING CALIBRATED GENE EXPRESSION PROFILES
WO/2001/032928	May, 2001			METHODS OF DETERMINING INDIVIDUAL HYPERSENSITIVITY TO AN AGENT
WO/2001/036684	May, 2001			MAMMALIAN TOXICOLOGICAL RESPONSE MARKERS
WO/2001/038579	May, 2001			METHOD OF IDENTIFYING TOXIC AGENTS USING NSAID-INDUCED DIFFERENTIAL GENE EXPRESSION IN LIVER
WO/2001/044512	June, 2001			METHOD OF IDENTIFYING LIGANDS FOR THE PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA USING DIFFERENTIAL GENE EXPRESSION
WO/2001/063279	August, 2001			METHOD OF IDENTIFYING TOXIC AGENTS USING DIFFERENTIAL GENE EXPRESSION
WO/2002/031704	April, 2002			INTERACTIVE CORRELATION OF COMPOUND INFORMATION AND GENOMIC INFORMATION
WO/2003/085083	October, 2003			LIVER NECROSIS PREDICTIVE GENES
WO/2003/095624	November, 2003			LIVER INFLAMMATION PREDICTIVE GENES
WO/2003/100030	December, 2003			KIDNEY TOXICITY PREDICTIVE GENES

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Smith, Carolyn L.

Cooley Godward Kronish LLP

RELATED APPLICATIONS

This is a divisional application of copending application Ser. No. 10/152,319, filed May 22, 2002, which claims priority to U.S. Provisional Applications 60/292,335, filed May 22, 2001; 60/297,523, filed Jun. 13, 2001; 60/298,925, filed Jun. 19, 2001; 60/303,810, filed Jul. 10, 2001; 60/303,807, filed Jul. 10, 2001; 60/303,808, filed Jul. 10, 2001; 60/315,047, filed Aug. 28, 2001; 60/324,928, filed Sep. 27, 2001; 60/330,867, filed Nov. 1, 2001; 60/330,462, filed Oct. 22, 2001; 60/331,805, filed Nov. 21, 2001; 60/336,144, filed Dec. 6, 2001; 60/340,873, filed Dec. 19, 2001; 60/357,843, filed Feb. 21, 2002; 60/357,842, filed Feb. 21, 2002; 60/357,844, filed Feb. 21, 2002; 60/364,134, filed Mar. 15, 2002; 60/370,206, filed Apr. 8, 2002; 60/370,247, filed Apr. 8, 2002; 60/370,144, filed Apr. 8, 2002; 60/371,679, filed Apr. 12, 2002 and 60/372,794, Apr. 17, 2002 all of which are herein incorporated by reference in their entirety. This application is also related to U.S. application Ser. Nos. 09/917,800 and 10/060,087, all of which are herein incorporated by reference in their entirety.

We claim:

1. A method for predicting the renal toxicity of a test compound, comprising: (a) preparing a normalized gene expression profile of at least ten genes for a rat kidney tissue or rat kidney cell sample, wherein the gene expression profile contains the differential gene expression values for said at least ten genes upon exposure to the test compound, and wherein said at least ten genes are listed in one of Tables 5-5CC; (b) comparing the gene expression profile to a renal toxicity model, the renal toxicity model comprising: (i) the normalized mean expression levels of said at least ten genes in kidney tissue or kidney cells exposed to a known renal toxin, and (ii) the normalized mean expression levels of said at least ten genes in unexposed kidney tissue or kidney cells; and (iii) information from one or more of Tables 5-5CC; (c) scoring the comparison to predict whether the test compound is a renal toxin; and (d) presenting the prediction.

2. The method of claim 1, wherein the gene expression profile comprises the levels of expression for at least 50 genes from Tables 5-5CC.

3. The method of claim 1, wherein the gene expression profile comprises the levels of expression for at least 100 genes from Tables 5-5CC.

4. The method of claim 1, wherein the kidney tissue or kidney cells are exposed to the test compound in vivo.

5. The method of claim 1, wherein the known renal toxin is associated with one or more of nephritis, kidney necrosis, glomerular or tubular injury, and focal segmental glomerulosclerosis.

6. The method of claim 1, wherein the known renal toxin is selected from the group consisting of cephaloridine, cisplatin, puromycin aminonucleoside (PAN), bromoethylamine hydrobromide (BEA), ifosfamide, cyclophosphamide, carboplatin, AY-25329, indomethacin, acyclovir, citrinin, mercuric chloride, diflunisal, cidofovir, pamidronate, lithium chloride, hydralazine, colchicine, sulfadiazine, captopril, semustine and adriamycin.

7. The method of claim 1, wherein the gene expression profile and the renal toxicity model are produced by hybridization of nucleic acids to a microarray.

8. The method of claim 1, wherein the scoring comprises determining whether the test compound induces a change in the expression of each of said at least ten genes in the same direction as the known renal toxin.

9. The method of claim 1, wherein preparing a normalized gene expression profile comprises hybridizing RNA from the kidney tissue or kidney cell sample to a panel of nucleic acid probes.

10. The method of claim 6, wherein the gene expression profile and the renal toxicity model are produced by hybridization of nucleic acids to a microarray.

11. The method of claim 6, wherein the scoring comprises determining whether the test compound induces a change in the expression of each of said at least ten genes in the same direction as the known renal toxin.

12. The method of claim 6, wherein preparing a normalized gene expression profile comprises hybridizing RNA from the kidney tissue or kidney cell sample to a panel of nucleic acid probes.

13. The method of claim 6, wherein said information from one or more of Tables 5-5CC are Tox and NonTox mean values.

14. The method of claim 6, wherein the renal toxicity model comprises the Tox and NonTox mean values in Tables 5-5CC.

SEQUENCE LISTING SUBMISSION ON COMPACT DISC

The Sequence Listing submitted concurrently herewith on compact disc under 37 C.F.R. §§1.821(c) and 1.821(e) is herein incorporated by reference in its entirety. Three copies of the Sequence Listing, one on each of three compact discs are provided. Copy 1 and Copy 2 are identical. Copies 1 and 2 are also identical to the CRF. Each electronic copy of the Sequence Listing was created on May 22, 2002 with a file size of 3088 KB. The file names are as follows: Copy 1- gl5089us.txt; Copy 2- gl5089us.txt; CRF- gl5089us.txt.

BACKGROUND OF THE INVENTION

The need for methods of assessing the toxic impact of a compound, pharmaceutical agent or environmental-pollutant on a cell or living organism has led to the development of procedures which utilize living organisms as biological monitors. The simplest and most convenient of these systems utilize unicellular microorganisms such as yeast and bacteria, since they are the most easily maintained and manipulated. In addition, unicellular screening systems often use easily detectable changes in phenotype to monitor the effect of test compounds on the cell. Unicellular organisms, however, are inadequate models for estimating the potential effects of many compounds on complex multicellular animals, as they do not have the ability to carry out biotransformations.

The biotransformation of chemical compounds by multicellular organisms is a significant factor in determining the overall toxicity of agents to which they are exposed. Accordingly, multicellular screening systems may be preferred or required to detect the toxic effects of compounds. The use of multicellular organisms as toxicology screening tools has been significantly hampered, however, by the lack of convenient screening mechanisms or endpoints, such as those available in yeast or bacterial systems. Additionally, previous attempts to produce toxicology prediction systems have failed to provide the necessary modeling data and statistical information to accurately predict toxic responses (e.g., WO 00/12760, WO 00/47761, WO 00/63435, WO 01/32928, and WO 01/38579).

SUMMARY OF THE INVENTION

The present invention is based on the elucidation of the global changes in gene expression in tissues or cells exposed to known toxins, in particular renal toxins, as compared to unexposed tissues or cells as well as the identification of individual genes that are differentially expressed upon toxin exposure.

In various aspects, the invention includes methods of predicting at least one toxic effect of a compound, predicting the progression of a toxic effect of a compound, and predicting the renal toxicity of a compound. The invention also includes methods of identifying agents that modulate the onset or progression of a toxic response. Also provided are methods of predicting the cellular pathways that a compound modulates in a cell. The invention also includes methods of identifying agents that modulate protein activities.

In a further aspect, the invention includes probes comprising sequences that specifically hybridize to genes in Tables 1-5. Also included are solid supports comprising at least two of the previously mentioned probes. The invention also includes a computer system that has a database containing information identifying the expression level in a tissue or cell sample exposed to a renal toxin of a set of genes comprising at least two genes in Tables 1-5.

DETAILED DESCRIPTION

Many biological functions are accomplished by altering the expression of various genes through transcriptional (e.g. through control of initiation, provision of RNA precursors, RNA processing, etc.) and/or translational control. For example, fundamental biological processes such as cell cycle, cell differentiation and cell death, are often characterized by the variations in the expression levels of groups of genes.

Changes in gene expression are also associated with the effects of various chemicals, drugs, toxins, pharmaceutical agents and pollutants on an organism or cell. For example, the lack of sufficient expression of functional tumor suppressor genes and/or the over expression of oncogene/protooncogenes after exposure to an agent could lead to tumorgenesis or hyperplastic growth of cells (Marshall (1991), Cell 64: 313-326; Weinberg (1991), Science 254: 1138-1146). Thus, changes in the expression levels of particular genes (e.g. oncogenes or tumor suppressors) may serve as signposts for the presence and progression of toxicity or other cellular responses to exposure to a particular compound.

Monitoring changes in gene expression may also provide certain advantages during drug screening and development. Often drugs are screened for the ability to interact with a major target without regard to other effects the drugs have on cells. These cellular effects may cause toxicity in the whole animal, which prevents the development and clinical use of the potential drug.

The present inventors have examined tissue from animals (kidney cells) exposed to known renal toxins which induce detrimental kidney effects, to identify global changes in gene expression induced by these compounds (Tables 5-5CC). These global changes in gene expression, which can be detected by the production of expression profiles (an expression level of one or more genes), provide useful toxicity markers that can be used to monitor toxicity and/or toxicity progression by a test compound. Some of these markers may also be used to monitor or detect various disease or physiological states, disease progression, drug efficacy, and drug metabolism.

Identification of Toxicity Markers

To evaluate and identify gene expression changes that are predictive of toxicity, studies using selected compounds with well characterized toxicity have been conducted by the present inventors to catalogue altered gene expression during exposure in vivo and in vitro. In the present study, cephaloridine, cisplatin, puromycin aminonucleoside (PAN), bromoethylamine hydrobromide (BEA), gentamicin, ifosfamide, cyclophosphamide, carboplatin, AY-25329, indomethacin, acyclovir, citrinin, mercuric chloride, diflunisal, cidofovir, pamidronate, lithium, hydralazine, colchicine, sulfadiazine, and adriamycin were selected as known renal toxins.

Cephaloridine is an amphoteric, semi-synthetic, broad-spectrum cephalosporin derived from cephalosporin C. Cephalosporins are β-lactam-containing antibiotics which prevent bacterial growth by inhibiting polymerization of the peptidoglycan bacterial cell wall. The linear glycan chains (composed of N-acetylglucosime and N-acetylmuramic acid) are cross-linked to each other by the coupling of short chains of several amino acids, the coupling resulting from the action of a transpeptidase. It is believed that cephalosporins act by blocking the activity of the transpeptidase ( Goodman & Gilman's The Pharmalogical Basis of Therapeutics 9 ^th ed. , J. G. Hardman et al. Eds., McGraw Hill, N.Y., 1996, pp. 1074-1075, 1089-1095).

Cephaloridine is administered intramuscularly and is used to treat infections of the respiratory tract, gastrointestinal tract and urinary tract, as well as infections of soft tissue, bones and joints. Noted adverse effects include hypersensitivity reactions (such as anaphylactic shock, urticaria and bronchospasm), gastrointestinal disturbances, candidiasis, and cardiovascular and blood toxicity, in particular, toxicity to the hematopoietic system (cells responsible for the formation of red and white blood cells and platelets).

Although cephaloridine may be nephrotoxic at high dosages, it is not as harmful to the kidneys as are the aminoglycosides and polymixins. High dosages of cephaloridine may cause acute renal tubular necrosis ( Cecil Textbook of Medicine. 20 ^th ed. part XII , p. 586, J. C. Bennett and F. Plum Eds., W.B. Saunders Co., Philadelphia, 1996) or drug-induced interstitial nephritis, which is accompanied by elevated IgE levels, fever, arthralgia and maculopapular rash. Renal biopsopy demonstrates edema and interstitial inflammatory lesions, mainly with lymphocytes, monocytes, eosinophils and plasma cells. Vasculitis of small vessels may develop, leading to necrotising glomerulonephritis (G. Koren, “The nephrotoxic potential of drugs and chemicals. Pharmacological basis and clinical relevance.,” Med Toxicol Adverse Drug Exp 4(1):59-72, 1989).

Cephaloridine has also been shown to reduce mitochondrial respiration and uptake of anionic succinate and carrier-mediated anionic substrate transport (Tune et al. (1990), J Pharmacol Exp Ther 252: 65-69). In a study of oxidative stress and damage to kidney tissue, cephaloridine depleted reduced glutathione (GSH) and produced oxidized glutathione (GSSG) in the renal cortex. This drug also inhibited glutathione reductase and produced malondialdehyde and conjugated dienes (Tune et al. (1989), Biochem Pharmacol 38: 795-802). Because cephaloridine is actively transported into the proximal renal tubule, but slowly transported across the lumenal membrane into the tubular fluid, high concentrations can accumulate and cause necrosis. Necrosis can be prevented by administering inhibitors of organic anion transport, although such treatment may be counterproductive, as cephaloridine is passed in and out of the kidney by the renal organic anion transport system (Tune et al. (1980), J Pharmacol Exp Ther 215: 186-190).

Cisplatin (Pt(NH ₃ ) ₂ (Cl) ₂ ), a broad-spectrum anti-tumor agent, is commonly used to treat tumors of the testicles, ovaries, bladder, skin, head and neck, and lungs (PDR 47 ^th ed., pp. 754-757, Medical Economics Co., Inc., Montvale, N.J., 1993; Goodman & Gilman's The Pharmalogical Basis of Therapeutics 9 ^th ed. , pp. 1269-1271, J. G. Hardman et al. Eds., McGraw Hill, N.Y., 1996). Cisplatin diffuses into cells and functions mainly by alkylating the N ⁷ of guanine, a highly reactive site, causing interstrand and intrastrand crosslinks in the DNA that are lethal to cells. The drug is not sensitive to the cell cycle, although its effects are most pronounced in S phase.

Because the drug is cleared from the body mainly by the kidneys, the most frequent adverse effect of cisplatin usage is nephrotoxicity, the severity of which increases with increasing dosage and treatment terms. Other adverse effects include renal tubule damage, myelosuppression (reduced numbers of circulating platelets, leukocytes and erythrocytes), nausea and vomiting, ototoxicity, serum electrolyte disturbances (decreased concentrations of magnesium, calcium, sodium, potassium and phosphate, probably resulting from renal tubule damage), increased serum concentrations of urea and creatinine, and peripheral neuropathies.

In one study on rats (Nonclercq et al. (1989), Exp Mol Pathol 51:123-140) administration of cisplatin or carboplatin induced renal injury, carboplatin causing less damage than cisplatin. The most prominent injury was to the straight portion of proximal renal tubule.

In another rat study (Goldstein et al. (1981), Toxicol Appl Pharmacol 60: 163-175) animals injected with cisplatin displayed decreased food intake as drug dosage increased. On day 2, the high-dose groups (10-15 mg/kg) exhibited a six or seven-fold elevation in BUN. On day 4, BUN elevation was noted in the 5 mg/kg group. An increase in urine volume was observed beginning on days 3-4, along with decreased urine osmolality in the low-dose groups (2.5 or 5 mg/kg). Another experiment on rats (Agarwal et al. (1995), Kidney Int 48: 1298-1307) showed that cisplatin treatment produced elevations in serum creatinine levels, which began on day 3 and progressed for the duration of the study.

PAN (C ₂₂ H ₂₉ N ₇ O ₅ ), an antibiotic produced by Streptomyces alboniger , inhibits protein synthesis and is commonly used experimentally on rats to mimic human minimal change disease. One study showed that PAN-injected rats demonstrated an increase in levels of serum non-esterified fatty acids, while the serum albumin concentration was negatively affected (Sasaki et al. (1999), Adv Exp Med Biol 467: 341-346).

In another rat study, an adenosine deaminase inhibitor prevented PAN nephrotoxicity, indicating that PAN toxicity is linked to adenosine metabolism (Nosaka et al. (1997), Free Radic Biol Med 22: 597-605). Another group showed that PAN, when administered to rats, led to proteinuria, a condition associated with abnormal amounts of protein in the urine, and renal damage, e.g. blebbing of glomerular epithelial cells, focal separation of cells from the glomerular basement membrane, and fusion of podocytes (Olson et al. (1981), Lab Invest 44: 271-279). In another study on rats, administration of PAN induced glomerular epithelial cell apoptosis in a dose- and time-dependent manner (Sanwal et al. (2001), Exp Mol Pathol 70: 54-64).

One study with PAN-injected rats (Koukouritaki et al. (1998), J Investig Med 46: 284-289) examined the changes in the expression of the proteins paxillin, focal adhesion kinase, and Rho, all of which regulate cell adhesion to the extracellular matrix. Paxillin levels increased steadily, peaked at day 9 after PAN injection, and then remained elevated even after proteinuria resolved. There was no observed change in expression of either focal adhesion kinase or Rho.

BEA, (C ₂ H ₆ BrN.HBr), is commonly used experimentally on rats to induce papillary necrosis and renal cortex damage, which is similar to human analgesic nephropathy. BEA-induced papillary necrosis in rats eventually leads to the onset of focal glomerular sclerosis and nephrotic proteinuria (Garber et al. (1999), Am J Kidney Dis 33: 1033-1039). Even at low doses (50 mg/kg), BEA can induce an apex limited renal papillary necrosis (Bach et al. (1983), Toxicol Appl Pharmacol 69: 333-344). In male Wistar rats, BEA administered at 100 mg/kg was shown to cause renal papillary necrosis within 24 hours (Bach et al. (1991), Food Chem Toxicol 29: 211-219). Additionally, Bach et al. showed that there was an increase in urinary triglycerides, and lipid deposits were seen by Oil Red O lipid staining in the cells of the collecting ducts and hyperplastic urothelia adjacent to the necrosed region.

It has also been shown that succinate and citrate concentrations are significantly lower in the urine of BEA-treated rats (Holmes et al. (1995), Arch Toxicol 70: 89-95). Moreover, BEA treatment induced glutaric and adipic aciduria, which is symptomatic of an enzyme deficiency in the acyl CoA dehydrogenases. The same study examined urinary taurine levels in desert mice, and in BEA-treated desert mice there was an increase in the urinary taurine level which is indicative of liver toxicity.

Another study on BEA-treated rats showed that there was an increase in the concentrations of creatine in the renal papilla and glutaric acid in the liver, renal cortex, and renal medulla as soon as 6 hours post-treatment (Garrod et al (2001), Magn Reson Med 45: 781-790).

Discovered and purified in the early 1960's, gentamicin is a broad-spectrum aminoglycoside antibiotic that is cidal to aerobic gram-negative bacteria and commonly used to treat infections, e.g., those of the urinary tract, lungs and meninges. As is typical for an aminoglycoside, the compound is made of two amino sugar rings linked to a central aminocyclitol ring by glycosidic bonds. Aminoglycosides are absorbed poorly with oral administration, but are excreted rapidly by the kidneys. As a result, kidney toxicity is the main adverse effect, although ototoxicity and neuromuscular blockade can also occur. Gentamicin acts by interfering with bacterial protein synthesis. This compound is more potent than most other antibacterial inhibitors of protein synthesis, which are merely bacteriostatic, and its effects on the body are, likewise, more severe ( Goodman & Gilman's The Pharmalogical Basis of Therapeutics 9 ^th ed. , pp. 1103-1115, J. G. Hardman et al. Eds., McGraw Hill, N.Y., 1996).

Aminoglycosides work rapidly, and the rate of bacterial killing is concentration-dependent. Residual bactericidal activity remains after serum concentration has fallen below the minimum inhibitory concentration (MIC), with a duration that is also dosage/concentration-dependent. The residual activity allows for once-a-day administration in some patients. These drugs diffuse into bacterial cells through porin channels in the outer membrane and are then transported across the cytoplasmic membrane via a membrane potential that is negative on the inside (Goodman & Gilman, supra).

Kidney damage, which can develop into renal failure, is due to the attack of gentamicin on the proximal convoluted tubule, particularly in the S1 and S2 segments. The necrosis, however, is often patchy and focal (Shanley et at (1990), Ren Fail 12: 83-87). A rat study by Shanley et al. showed that superficial nephrons are more susceptible to necrosis than juxtamedullary nephrons, although the initial segment of the superficial nephrons is remarkably resistant to necrosis.

Reported enzymatic changes upon gentamicin treatment are increased activities of N-acetyl-beta-D-glucosaminidase and alkaline phosphatase and decreased activities of sphingomyelirase, cathepsin B, Na ⁺ /K ⁺ -ATPase, lactate dehydrogenase and NADPH cytochrome C reductase, along with decreased protein synthesis and alpha-methylglucose transport (Monteil et al. (1993), Ren Fail 15: 475-483). An increase in gamma-glutamyl transpeptidase activity in urine has also been reported (Kocaoglu et al. (1994), Arch Immunol Ther Exp ( Warsz ) 42: 125-127), and the quantification of this enzyme in urine is a useful marker for monitoring gentamicin toxicity.

One source of renal pathology resulting from gentamicin treatment is the generation of reactive oxygen metabolites. Gentamicin has been shown, both in vitro and in vivo, to be capable of enhancing the production of reactive oxygen species. Iron, a necessary co-factor that catalyzes free-radical formation, is supplied by cytochrome P450 (Baliga et al. (1999), Drug Metab Rev 31: 971-997).

A gene delivery experiment in rats, in which the human kallikrein gene was cloned into an adenovirus vector and the construct then co-administered with a gentamicin preparation, showed that kallikrein can protect against gentamicin-induced nephrotoxicity. Significantly increased renal blood flow, glomerular filtration rates and urine flow were observed, along with decreased renal tubular damage, cellular necrosis and lumenal protein casts. Kallikrein gene delivery also caused a decrease in blood urea nitrogen levels and increases in urinary kinin and nitrite/nitrate levels. This study provides evidence that the tissue kallikrein-kinin system may be a key pathway that is perturbed during the induction of nephrotoxicity by gentamicin (Murakami et al. (1998), Kidney Int 53: 1305-1313).

Ifosfamide, an alkylating agent, is commonly used in chemotherapy to treat testicular, cervical, and lung cancer. Ifosfamide is slowly activated in the liver by hydroxylation, forming the triazene derivative 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed . p. 1235, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996). Cytochrome P450 activates DTIC via an N-demethylation reaction yielding an alkylating moiety, diazomethane. The active metabolites are then able to cross-link DNA causing growth arrest and cell death. Though ifosfamide is therapeutically useful, it is also associated with nephrotoxicity, urotoxicity, and central neurotoxicity.

Mesna, another therapeutic, is often administered concomitantly to prevent kidney and bladder problems from arising (Brock and Pohl (1986), IARC Sci Publ 78: 269-279). However, there are documented cases in which tubular toxicity occurred and elevated urinary levels of alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase were found in patients even though mesna was administered alongside ifosfamide (Goren et al. (1987), Cancer Treat Rep 71: 127-130).

One study examined 42 patients that had been administered ifosfamide to treat advanced soft-tissue sarcoma (Stuart-Harris et al. (1983), Cancer Chemother Pharmacol 11: 69-72). The ifosfamide dosage varied from 5.0 g/m ² to 8.0 g/m ² , and all of the patients were given mesna to counteract the negative effects of ifosfamide. Even so, nausea and vomiting were common to all of the patients. Out of the 42 patients, seven developed nephrotoxicity, and two of the cases progressed to fatal renal failure.

In another clinical study, renal tubular function was monitored in 18 neuroblastoma patients (Caron et al. (1992), Med Pediatr Oncol 20: 42-47). Tubular toxicity occurred in at least 12 of the patients, and seven of those patients eventually developed Debre-de Toni-Fanconi syndrome, although in 3 cases the syndrome was reversible.

Fanconi syndrome is a disorder marked by dysfunction of the proximal tubules of the kidney. It is associated with aminoaciduria, renal glycosuria, and hyperphosphaturia. Ifosfamide is often used experimentally on rats to induce Fanconi syndrome. In one study, rats that were administered 80 mg/kg of ifosfamide had significantly lower body weight and hematocrit than control rats (Springate and Van Liew (1995), J Appl Toxicol 15: 399-402). Additionally, the rats had low-grade glucosuria, proteinuria, and phosphaturia. In a mouse study, ifosfamide induced elevated serum creatinine and urea levels and decreased the clearance rate of creatinine (Badary (1999), J Ethnopharmacol 67: 135-142).

Cyclophosphamide, a nitrogen mustard and alkylating agent, is highly toxic to dividing cells and is commonly used in chemotherapy to treat malignant lymphomas, such as non-Hodgkin's lymphomas and Burkitt's lymphoma, multiple myeloma, leukemias, neuroblastomas, ovarian adenocarcinomas and retinoblastomas, as well as breast and lung cancer ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed., pp. 1234, 1237-1239, J. G. Hardman et al., eds., McGraw Hill, N.Y., 1996; Physicians Desk Reference, 47 ^th ed., pp. 744-745, Medical Economics Co., Inc., Montvale, N.J., 1993). Additionally, cyclophosphamide is used as an immunosuppressive agent in bone marrow transplantation and following organ transplantation. Although cyclophosphamide is therapeutically useful against certain types of cancer, it is also associated with cardiotoxicity, nephrotoxicity (including renal tubular necrosis), hemorrhagic cystitis, myelosuppression, hepatotoxicity, impairment of male and female reproductive systems, interstitial pneumonitis and central nervous system toxicity.

Once in the liver, cyclophosphamide is hydroxylated by the cytochrome P450 mixed function oxidase system, producing the active metabolites phosphoramide mustard and acrolein, which cross-link DNA and cause growth arrest and cell death. These metabolites, however, are highly toxic and cause adverse effects in the other organs into which they are transported, such as the kidneys. Acrolein is removed from the kidneys by secretion into the urine, resulting in cystitis (inflammation of the bladder), often hemorrhagic cystitis.

In the kidney, cyclophosphamide induces necrosis of the renal distal tubule. Cyclophosphamide, which is structurally similar to the anti-cancer drug ifosfamide, does not induce damage to the renal proximal tubule nor does it induce Debre-de Toni-Fanconi syndrome (Rossi et al. (1997), Nephrol Dial Transplant 12: 1091-1092).

One clinical trial of patients being treated with cyclophosphamide showed that renal damage from the drug leads to a reduced biotransformation rate and low renal clearance of the drug, resulting in a build-up of toxic alkylating metabolic products (Wagner et al. (1980), Arzneimittelforschung 30: 1588-1592).

In a study of patients suffering from malignant lymphomas and mammary carcinomas, a direct relationship was found between the dose of cyclophosphamide used in treatment and the concentration of alkylating metabolites in the patients' urine. The upper limit of the dose was determined by the nature and degree of the toxic side effects, rather than by the rate at which the drug could be metabolized (Saul et al. (1979), J Cancer Res Clin Oncol 94: 277-286). It is the acrolein itself that is toxic, not the alkylating activity of cyclophosphamide (Brock et al. (1979), Arzneimittelforschung 29: 659-661). A study on rats also showed that acrolein from the kidneys can produce hemorrhagic cystitis and that the acrolein concentration is directly related to the frequency and severity of the cystitis (Chijiwa et al. (1983), Cancer Res 43: 5205-5209).

Carboplatin, a platinum coordination complex, is commonly used in chemotherapy as an anti-tumor agent. As a chemotherapeutic agent, carboplatin acts similarly to cisplatin. Carboplatin enters the cell by diffusion where it is activated by hydrolysis ( Goodman & Gilman's The Pharmacoloiical Basis of Therapeutics 9 ^th ed. , p. 1270-1271, J. G. Hardman et al. Eds., McGraw Hill, N.Y. 1996). Once activated, the platinum complexes are able to react with DNA causing cross-linking to occur. One of the differences between carboplatin and cisplatin is that carboplatin is better tolerated clinically. Some of the side-effects associated with cisplatin, such as nausea, neurotoxicity, and nephrotoxicity, are seen at a lesser degree in patients administered carboplatin. Some other side-effects are hypomagnesaemia and hypokalaemia (Kintzel (2001), Drug Saf 24: 19-38).

In one study on male Wistar rats, carboplatin was administered at a dosage of 65 mg/kg (Wolfgang et al. (1994), Fundam Appl Toxicol 22: 73-79). After treatment with carboplatin, CGT excretion was increased approximately two-fold.

Another study compared cisplatin and carboplatin when given in combination with vindesine and mitomycin C (Jelic et al. (2001) Lung Cancer 34: 1-13). The study showed that carboplatin administered with vindesine and mitomycin C was advantageous in terms of overall survival, although the regimen was more hematologically toxic than when cisplatin was given.

AY-25329, is a phenothiazine that has been shown to be mildly hepatotoxic and to induce nephrosis. Its structure is shown below.

Phenothiazines are a class of psychoactive drugs. They have been used to treat schizophrenia, paranoia, mania, hyperactivity in children, some forms of senility, and anxiety. Some side effects associated with prolonged use of the drugs are reduced blood pressure, Parkinsonism, reduction of motor activity, and visual impairment.

Chlorpromazine (Thorazine or Largactil) is an aliphatic phenothiazine and is widely used for treating schizophrenia and manic depression. Prolactin secretion is increased while taking chlorpromazine, and galactorrhea and gynecomastia have both been associated with the drug. Trifluoperazine is another prescribed phenothiazine. It is used to treat anxiety, to prevent nausea and vomiting, and to manage psychotic disorders. Negative side-effects that have been associated with the drug are liver damage, bone marrow depression, and Parkinsonism.

Acyclovir (9-[(2-hydroxyethyl)methyl]guanine, Zovirax®), an anti-viral guanosine analogue, is used to treat herpes simplex virus (HSV), varicella zoster virus (VZV) and Epstein-Barr virus (EBV) infections. It is transported into cells by the nucleoside transporter that imports guanine, and acyclovir is phosphorylated by virally encoded thymidine kinase (TK). Other kinases convert acyclovir to its activated di- and triphosphate forms, which prevent the polymerization of viral DNA. Acyclovir triphosphate competes with dGTP for the viral polymerase, and acyclovir is preferentially incorporated, but as a monophosphate. As a result, chain elongation ceases ( Fields Virology 3d ed., Fields et al., eds., pp. 436-440, Lippincott-Raven Publishers, Philadelphia, 1996 ; Cecil Textbook of Medicine. 20 ^th ed. , part XII, p. 1742, J. C. Bennett and F. Plum Eds., W.B. Saunders Co., Philadelphia, 1996).

The pharmacokinetics of acyclovir show that it has a useful half-life of about three hours and that most of it is excreted in the urine largely unchanged (Brigden et al. (1985), Scand J Infect Dis Suppl 47:33-39). Not surprisingly, the most frequent adverse effect of acyclovir treatment is damage to various parts of the kidney, particularly the renal tubules. Crystalluria, or the precipitation of crystals (in this case, crystals of acyclovir), in the lumina of the renal tubules can occur (Fogazzi (1996), Nephrol Dial Transplant 11: 379-387). If the drug crystallizes in the renal collecting tubules, obstructive nephropathy and tubular necrosis can result (Richardson (2000), Vet Hum Toxicol 42: 370-371). Tissues from biopsies of affected patients showed dilation of the proximal and distal renal tubules, with loss of the brush border, flattening of the lining cells and focal nuclear loss (Becker et al. (1993), Am J Kidney Dis 22: 611-615).

Citrinin, a mycotoxin produced by the fungus Penicillium citrinum , is a natural contaminant of foods and feeds (Bondy and Armstrong (1998) Cell Biol. Toxicol. 14: 323-332). It is known that mycotoxins can have negative effects on the immune system, however citrinin-treated animals have been shown to stimulate responses against antigens (Sharma (1993) J. Dairy Sci. 76: 892-897). Citrinin is a known nephrotoxin, and in birds such as chickens, ducklings, and turkeys, it causes diarrhea, increased food consumption and reduced weight gain due to kidney degeneration (Mehdi et al. (1981) Food Cosmet. Toxicol. 19: 723-733; Mehdi et al. (1984) Vet. Pathol. 21: 216-223). In the turkey and duckling study, both species exhibited nephrosis with the occurrence of hepatic and lymphoid lesions (Mehdi et al., 1984).

In one study, citrinin was administered to rabbits as a single oral dose of either 120 or 67 mg/kg (Hanika et al. (1986) Vet. Pathol. 23: 245-253). Rabbits treated with citrinin exhibited renal alterations such as condensed and distorted mitochondria, distended intercellular spaces of the medullary and straight cortical distal tubules, and disorganization of interdigitating processes. In another rabbit study, citrinin-administered rabbits displayed azotaemia and metabolic acidosis (Hanika et al. (1984) Food Chem. Toxicol. 22: 999-1008). Renal failure was indicated by decreased creatinine clearance and increased blood urea nitrogen and serum-creatinine levels.

In the past, mercury was an important component of pharmaceuticals, particularly of antiseptics, antibacterials, skin ointments, diuretics and laxatives. Although, mercury has been largely replaced by more effective, more specific and safer compounds, making drug-induced mercury poisoning rare, it is still widely used in industry. Poisoning from occupational exposure and environmental pollution, such as mercury release into public water supplies, remains a concern as wildlife, domestic animals and humans are affected.

Because of their lipid solubility and ability to cross the blood-brain barrier, the most dangerous form of mercury is the organomercurials, the most common of which is methylmercury, a fungicide used for disinfecting crop seeds. In a number of countries, incidents involving large-scale illness and death from mercury poisoning have been reported when mercury-contaminated seeds were planted and the crops harvested and consumed. A second source of organic mercury poisoning results from industrial chemicals containing inorganic mercury, such as mercury catalysts, which form methylmercury as a reaction product. If this waste product is released into reservoirs, lakes, rivers or bays, the surrounding population can become sick or die, particularly those who eat local fish.

The inorganic salt mercuric chloride, HgCl ₂ , as well as other mercuric salts, are more irritating and more toxic than the mercurous forms. Mercuric chloride is used today in industry, for the manufacture of bleach, electronics, plastics, fungicides and dental amalgams. The main source of human exposure is industrial dumping into rivers (Goodman & Gilman's: The Pharmacological Basis of Therapeutics (9th ed.), pp. 1654-1659, McGraw-Hill, N.Y., 1996).

When inorganic mercury salts are ingested, about 10% of the mercuric ions are absorbed by the gastrointenstinal tract, and a considerable portion of the Hg ²⁺ can remain bound to the mucosal surfaces. The highest concentration of Hg ²⁺ is found in the kidneys, as it is retained there longer than in other tissues. Consequently, the kidneys are the organ most adversely affected by inorganic mercury poisoning. The proximal tubules are the major site of damage, where tubular necrosis results. The mercury affects primarily the S2 and S3 portions of the proximal tubules, but, at high levels of mercury exposure, the S1 and distal portions of the tubules are also damaged. These regions of the nephrons are affected because they contain enzymes (such as gamma-glutamyltranspeptidase) and transport proteins (such as the basolateral organic anion transport system) involved in mercury uptake (Diamond et al. (1998), Toxicol Pathol 26: 92-103).

Urinary markers of mercury toxicity which can be detected in NMR spectra include elevated levels of lactate, acetate and taurine and decreased levels of hippurate (Holmes et al (2000), Chem Res Toxicol 13: 471-478). Known changes in gene expression in kidneys exposed to Hg ²⁺ include up-regulation of the heat-shock protein hsp72 and of the glucose-regulated protein grp94. The degree of tissue necrosis and level of expression of these proteins is proportional to both the dose of mercury (Hg ²⁺ ) and the length of the exposure time to mercury (Hg ²⁺ ), with hsp72 accumulating in the renal cortex and grp94 accumulating in the renal medulla (Goering et al. (2000), Toxicol Sci 53: 447-457).

Diflunisal, a non-steroidal anti-inflammatory drug (NSAID), is a difluorophenyl derivative of salicylic acid ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed . p. 631, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996). It is most frequently used in the treatment of osteoarthritis and musculoskeletal strains. NSAIDs have analgesic, antipyretic and anti-inflammatory actions, however hepatotoxicity is known to be an adverse side effect of NSAID treatment (Masubuchi et al. (1998) J. Pharmacol. Exp. Ther. 287: 208-213). Diflunisal has been shown to be less toxic than other NSAIDs, nevertheless over long periods of dosage it can lead to deleterious effects on platelet or kidney function (Bergamo et al. (1989) Am. J. Nephrol. 9: 460-463). Other side effects that have been associated with diflunisal treatment are diarrhea, dizziness, drowsiness, gas or heartburn, headache, nausea, vomiting, and insomnia.

Masubuchi et al. compared the hepatotoxicity of 18 acidic NSAIDs. In the study, diflunisal (administered at a concentration of 500 μM) was shown to increase LDH leakage in rat hepatocytes, a marker for cell injury, when compared to the control sample. In addition, treatment with diflunisal led to decreased intracellular ATP concentrations.

One study compared the effects of diflunisal and ibuprofen when given to patients over a two week period (Muncie and Nasrallah (1989) Clin. Ther. 11: 539-544). In both the ibuprofen and the diflunisal group, two patients complained of abdominal cramping. The study indicated that even during short-term usage some gastrointestinal effects may occur. The toxic dose used in this study was chosen as one that did not induce significant gastric ulceration in rats. The group of rats given the high dosage of diflunisal had increased concentrations of creatinine which is consistent with renal injury, although dehydration may also cause increases in creatinine concentration.

Cidofovir (Vistide®) is an antiviral cytosine analog used in the treatment of viral infections such as herpesvirus, adenovirus, papillomavirus, poxvirus and hepadnavirus ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed. , p. 1216, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996). It is also useful for the treatment of cytomegalovirus (CMV) infection, which is a type of herpesvirus.

Some mild side effects seen in patients receiving cidofovir are nausea, vomiting, and fever. The most serious reported side effect of the drug is kidney toxicity. In response to the threat of nephrotoxicity, it is necessary for patients receiving cidofovir to have their kidneys checked before treatment, and the patients must be monitored during treatment for early symptoms of kidney problems. In addition, cidofovir is given with fluids to help reduce the risk of kidney toxicity. Probenecid, a drug that helps protect the kidneys, is normally administered concomitantly (Lalezari and Kuppermann (1997) J. Acquir. Immune Defic. Syndr. Hum. Retrovirol . 14: S27-31).

One study compared the safety and efficacy of cidofovir in the treatment of CMV (Lalezari et al. (1998) J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 17: 339-344). Approximately 40% of the patients exhibited dose-dependent asymptomatic proteinuria and 25% of the patients had elevated serum creatinine levels.

Pamidronate (Aredia®) is a bisphosphonate drug that is clinically used to inhibit bone resorption and make bones more stable. It is used to treat hypercalcemia (too much calcium in the blood) that occurs with some types of cancer. Typically administered by intravenous injection, pamidronate is frequently used in patients with breast cancer or multiple myeloma whose disease has spread to the bones. Some side effects related to pamidronate treatment are abdominal cramps, chills, confusion, fever, muscle spasms, nausea, muscle stiffness, and swelling at the injection site. Patients with kidney problems may be prohibited from using pamidronate as it is excreted through the kidneys.

In one study, rats and mice were given varying doses of labeled pamidronate (Cal and Daley-Yates (1990) Toxicology 65: 179-197). Pamidronate treatment led to significant weight loss and a decrease in creatinine clearance. Morphological studies showed a loss of brush border membranes and the presence of focal proximal tubular necrosis.

Another study compared the tolerability of different treatments for hypercalcemia of malignancy by reviewing articles published between 1979 and 1998 (Zojer et al. (1999) Drug Saf 21: 389-406). The authors found that elevated serum creatinine level, nausea, and fever were reported following treatment with bisphosphonates such as pamidronate.

Markowitz et al. (2001 , J. Am. Soc. Nephrol. 12: 1164-1172) tried to determine whether there was a correlation between pamidronate treatment and collapsing focal segmental glomerulosclerosis (FSGS). The authors examined the histories of seven patients who had developed collapsing FSGS, and they found that the only drug treatment in common was the administration of pamidronate. When given at the recommended dose of 90 mg per month, renal toxicity was rare. However, when pamidronate was given at higher doses nephrotoxicity occurred.

Lithium, an alkali metal, is the main pharmacological treatment for bipolar disorders. It is typically given as a salt, such as lithium carbonate or lithium citrate. Some common side effects of lithium treatment are an increase in urination, increase in drinking, dry mouth, weight gain, fine tremor, and fatigue. Some more serious side effects related to lithium treatment are blurred vision, mental confusion, seizures, vomiting, diarrhea, muscle weakness, drowsiness, and coarse tremor ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed. , p. 448, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996).

Since lithium is often used on a maintenance basis for a lifelong period, numerous studies have been performed to try and elucidate the effects of lithium on the kidney. One group administered lithium in daily doses within the human therapeutic range to male Wistar rats (Kling et al. (1984) Lab Invest 50: 526-535). Rats that were given lithium developed marked polyuria within three weeks of the initial dosing. The rats displayed elevated free water clearance and vasopressin-resistant diabetes insipidus. The cortical collecting tubules displayed morphological changes, e.g. dilation of the tubules, bulging cells lining the tubules, enlarged nuclei, following lithium treatment.

Another study examined a human population that had been given lithium for the treatment of bipolar disorder (Markowitz et al. (2000) J. Am. Soc. Nephrol. 11: 1439-1448). The patients had a mean age of 42.5 years and had been undergoing lithium treatment from 2 to 25 years (mean of 13.6 years). Approximately one fourth of the patients had nephrotic proteinuria, almost 90% of them had nephrogenic diabetes insipidus (NDI), and renal biopsies revealed a chronic tubulointerstitial nephropathy in all of the patients. Following cessation of lithium treatment, seven of the patients proceeded to end-stage renal disease.

Even though nephrotoxicity is a known side effect of lithium treatment, some studies have indicated that in actuality it is not all that common (Johnson (1998) Neuropsychopharmacology 19: 200-205). One study showed that the NDI-like effect in lithium treatment was easily overcome by increasing the levels of arginine vasopressin (AVP) (Carney et al. (1996) Kidney Int 50: 377-383). Other studies have suggested that patients with psychiatric disorders display certain defects in renal function without undergoing lithium treatment (Gitlin (1999) Drug Saf 20: 231-243).

Hydralazine, an antihypertensive drug, causes relaxation of arteriolar smooth muscle. Such vasodilation is linked to vigorous stimulation of the sympathetic nervous system, which in turn leads to increased heart rate and contractility, increased plasma renin activity, and fluid retention ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed. , p. 794, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996). The increased renin activity leads to an increase in angiotensin 11, which in turn causes stimulation of aldosterone and sodium reabsorption.

Hydralazine is used for the treatment of high blood pressure (hypertension) and for the treatment of pregnant women suffering from high blood pressure (pre-eclampsia or eclampsia). Some common side effects associated with hydralazine use are diarrhea, rapid heartbeat, headache, decreased appetite, and nausea. Hydralazine is often used concomitantly with drugs that inhibit sympathetic activity to combat the mild pulmonary hypertension that can be associated with hydralazine usage.

In one hydralazine study, rats were fed hydralazine and mineral metabolism was monitored (Peters et al. (1988) Toxicol Lett 41: 193-202). Manganese and zinc concentrations were not effected by hydralazine treatment, however tissue iron concentrations were decreased and kidney copper concentrations were increased compared to control groups.

Another study compared the effects of hydrazine, phenelzine, and hydralazine treatment on rats (Runge-Morris et al. (1996) Drug Metab Dispos 24: 734-737). Hydralazine caused an increase in renal GST-alpha subunit expression, although unlike hydrazine and phenelzine it did not alter renal cytochrome P4502E1 expression.

Colchicine, an alkoloid of Colchicum autumale , is an antiinflammatory agent used in the treatment of gouty arthritis ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed. , p. 647, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996).

An antimitotic agent, colchicine binds to tubulin which leads to depolymerization and disappearance of the fibrillar microtubules in granulocytes and other motile cells. In doing so, the migration of granulocytes into the inflamed area is inhibited. Through a series of events, the inflammatory response is blocked.

Some common, mild side effects associated with colchicine treatment are loss of appetite and hair loss. More severe side effects that warrant cessation of treatment are nausea, vomiting, diarrhea, and abdominal pain. Coichicine overdose can induce multiorgan failure with a high incidence of mortality. In this setting, renal failure is multifactorial and related to prolonged hypotension, hypoxemia, sepsis, and rhabdomyolysis. In rats, less dramatic doses have been shown to inhibit the secretion of many endogenous proteins such as insulin and parathyroid hormone.

One study investigated the effects of colchicine on microtubule polymerization status and post-translational modifications of tubulin in rat seminiferous tubules (Correa and Miller (2001) Biol Reprod 64: 1644-1652). Colchicine caused extensive microtubule depolymerization, and total tubulin levels decreased twofold after coichicine treatment. The authors also found that colchicine treatment led to a decrease in tyrosination of the microtubule pool of tubulin which was associated with depolymerization of microtubules.

Sulfadiazine, a sulfonamide, is an antimicrobial agent. It is commonly used concomitantly with pyrimethamine to treat toxoplasmosis, an infection of the brain, in patient suffering from AIDS. These drugs are able to cross the blood-brain barrier and are used at relatively high doses. In addition, sulfadiazine has been shown to be effective at preventing certain types of meningococcal diseases and in treating urinary tract infections.

Sulfonamides in general are structural analogs of para-aminobenzoic acid (PABA). Because they are competitive antagonists of PABA, sulfonamides are effective against bacteria that are required to utilize PABA for the synthesis of folic acid ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed. , p. 1058-1060, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996).

The main side effects associated with sulfadiazine treatment are fever and skin rashes. Decreases in white blood cells, red blood cells, and platelets, nausea, vomiting, and diarrhea are some other side effects that may result from sulfadiazine treatment. The most troublesome problem with this drug for HIV/AIDS patients is kidney toxicity. These patients tend to use these drugs for extended periods of time, which puts a constant strain on the kidneys. In addition, kidney stones tend to form in the bladder and ureter thereby blocking the flow of urine. Kidney damage may result, and if left untreated kidney failure may occur. Therefore, patients being treated with sulfadiazine are instructed to increase their fluid intake in order to prevent crystal formation in the kidneys.

One case study examined four HIV-positive patients who had been given sulfadiazine to treat toxoplasmosis (Crespo et al. (2000) Clin Nephrol 54: 68-72). All four of the patients, one of whom was a previously healthy person, developed oliguria, abdominal pain, renal failure, and displayed multiple radiolucent renal calculi in echography. Following extensive hydration and alcalinization, the renal function of the patients returned to normal.

Adriamycin, known generically as doxorubicin, is an anthracycline antibiotic produced by the fungus Streptomyces peucetius . It is an anti-tumor drug used in the treatment of breast, ovarian, bladder, and lung cancers as well as non-Hodgkin's lymphoma, Hodgkin's disease and sarcoma ( Goodman & Gilman's The Pharmacological Basis of Therapeutics 9 ^th ed. , p. 1264-1265, J. G. Hardman et al., Eds., McGraw Hill, N.Y., 1996).

Adriamycin has tetracycline ring structures with the sugar daunosamine attached by glycosidic linkage. It is able to intercalate with DNA, it affects DNA and RNA synthesis, and it can interact with cell membranes and alter their functions. Typically the drug is cell-cycle specific for the S phase of cell division. By binding to the cancer cells' DNA and blocking topoisomerase II, cancer cells are unable to divide and grow.

Some common side effects associated with adriamycin treatment are fatigue, a drop in white blood cell, red blood cell, or platelet count, hair loss, skin discoloration, and watery eyes. More serious side effects include myocardial toxicity, ulceration and necrosis of the colon, and development of a second cancer.

Because of its utility in fighting cancer, numerous studies have been performed in attempts to further understand the mechanisms and effects of adriamycin. In one study, investigators injected mice with a single dose of adriamycin (Chen et al. (1998) Nephron 78: 440-452). The mice exhibited signs of combined glomerular albuminuria and immunoglublinuria, progressively elevated levels of nitrite/nitrate in the urine, abnormal renal function, and other symptoms indicative of focal segmental glomerulosclerosis.

In another study, rats were given adriamycin and the effects on angiotensin converting enzyme (ACE) were monitored (Venkatesan et al. (1993) Toxicology 85: 137-148). The rats developed glomerular and tubular injury, and serum ACE levels were significantly elevated 20, 25, and 30 days post-treatment. A different study followed rabbits for up to one year that were treated with either adriamycin, nephrectomy, or combinations thereof (Gadeholt-Gothlin et al. (1995) Urol Res 23: 169-173). The rabbits that were treated with adriamycin exhibited signs of nephrotoxicity at relatively low doses.

Toxicity Prediction and Modeling

The genes and gene expression information, gene expression profiles, as well as the portfolios and subsets of the genes provided in Tables 1-5, may be used to predict at least one toxic effect, including the nephrotoxicity of a test or unknown compound. As used, herein, at least one toxic effect includes, but is not limited to, a detrimental change in the physiological status of a cell or organism. The response may be, but is not required to be, associated with a particular pathology, such as tissue necrosis. Accordingly, the toxic effect includes effects at the molecular and cellular level. Nephrotoxicity is an effect as used herein and includes but is not limited to the pathologies of nephritis, kidney necrosis, glomerular and tubular injury, and focal segmental glomerulosclerosis. As used herein, a gene expression profile comprises any quantitative representation of the expression of at least one mRNA species in a cell sample or population and includes profiles made by various methods such as differential display, PCR, hybridization analysis, etc.

In general, assays to predict the toxicity or nephrotoxicity of a test agent (or compound or multi-component composition) comprise the steps of exposing a cell population to the test compound, assaying or measuring the level of relative or absolute gene expression of one or more of the genes in Tables 1-5 and comparing the identified expression level(s) to the expression levels disclosed in the Tables and database(s) disclosed herein. Assays may include the measurement of the expression levels of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 50, 75, 100 or more genes from Tables 1-5.

In the methods of the invention, the gene expression level for a gene or genes induced by the test agent, compound or compositions may be comparable to the levels found in the Tables or databases disclosed herein if the expression level varies within a factor of about 2, about 1.5 or about 1.0 fold. In some cases, the expression levels are comparable if the agent induces a change in the expression of a gene in the same direction (e.g., up or down) as a reference toxin.

The cell population that is exposed to the test agent, compound or composition may be exposed in vitro or in vivo. For instance, cultured or freshly isolated renal cells, in particular rat renal cells, may be exposed to the agent under standard laboratory and cell culture conditions. In another assay format, in vivo exposure may be accomplished by administration of the agent to a living animal, for instance a laboratory rat.

Procedures for designing and conducting toxicity tests in in vitro and in vivo systems are well known, and are described in many texts on the subject, such as Loomis et al., Loomis's Esstentials of Toxicology, 4th Ed., Academic Press, New York, 1996; Echobichon, The Basics of Toxicity Testing, CRC Press, Boca Raton, 1992; Frazier, editor, In Vitro Toxicity Testing, Marcel Dekker, New York, 1992; and the like.

In in vitro toxicity testing, two groups of test organisms are usually employed: One group serves as a control and the other group receives the test compound in a single dose (for acute toxicity tests) or a regimen of doses (for prolonged or chronic toxicity tests). Because, in some cases, the extraction of tissue as called for in the methods of the invention requires sacrificing the test animal, both the control group and the group receiving compound must be large enough to permit removal of animals for sampling tissues, if it is desired to observe the dynamics of gene expression through the duration of an experiment.

In setting up a toxicity study, extensive guidance is provided in the literature for selecting the appropriate test organism for the compound being tested, route of administration. dose ranges, and the like. Water or physiological saline (0.9% NaCl in water) is the solute of choice for the test compound since these solvents permit administration by a variety of routes. When this is not possible because of solubility limitations, vegetable oils such as corn oil or organic solvents such as propylene glycol may be used.

Regardless of the route of administration, the volume required to administer a given dose is limited by the size of the animal that is used. It is desirable to keep the volume of each dose uniform within and between groups of animals. When rats or mice are used, the volume administered by the oral route generally should not exceed about 0.005 ml per gram of animal. Even when aqueous or physiological saline solutions are used for parenteral injection the volumes that are tolerated are limited, although such solutions are ordinarily thought of as being innocuous. The intravenous LD ₅₀ of distilled water in the mouse is approximately 0.044 ml per gram and that of isotonic saline is 0.068 ml per gram of mouse. In some instances, the route of administration to the test animal should be the same as, or as similar as possible to, the route of administration of the compound to man for therapeutic purposes.

When a compound is to be administered by inhalation, special techniques for generating test atmospheres are necessary. The methods usually involve aerosolization or nebulization of fluids containing the compound. If the agent to be tested is a fluid that has an appreciable vapor pressure, it may be administered by passing air through the solution under controlled temperature conditions. Under these conditions, dose is estimated from the volume of air inhaled per unit time, the temperature of the solution, and the vapor pressure of the agent involved. Gases are metered from reservoirs. When particles of a solution are to be administered, unless the particle size is less than about 2 μm the particles will not reach the terminal alveolar sacs in the lungs. A variety of apparatuses and chambers are available to perform studies for detecting effects of irritant or other toxic endpoints when they are administered by inhalation. The preferred method of administering an agent to animals is via the oral route, either by intubation or by incorporating the agent in the feed.

When the agent is exposed to cells in vitro or in cell culture, the cell population to be exposed to the agent may be divided into two or more subpopulations, for instance, by dividing the population into two or more identical aliquots. In some preferred embodiments of the methods of the invention, the cells to be exposed to the agent are derived from kidney tissue. For instance, cultured or freshly isolated rat renal cells may be used.

The methods of the invention may be used generally to predict at least one toxic response, and, as described in the Examples, may be used to predict the likelihood that a compound or test agent will induce various specific kidney pathologies, such as nephritis, kidney necrosis, glomerular and tubular injury, focal segmental glomerulosclerosis, or other pathologies associated with at least one of the toxins herein described. The methods of the invention may also be used to determine the similarity of a toxic response to one or more individual compounds. In addition, the methods of the invention may be used to predict or elucidate the potential cellular pathways influenced, induced or modulated by the compound or test agent due to the similarity of the expression profile compared to the profile induced by a known toxin (see Tables 5-5CC).

Diagnostic Uses for the Toxicity Markers

As described above, the genes and gene expression information or portfolios of the genes with their expression information as provided in Tables 1-5 may be used as diagnostic markers for the prediction or identification of the physiological state of tissue or cell sample that has been exposed to a compound or to identify or predict the toxic effects of a compound or agent. For instance, a tissue sample such as a sample of peripheral blood cells or some other easily obtainable tissue sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables 1-5 may be compared to the expression levels found in tissues or cells exposed to the toxins described herein. These methods may result in the diagnosis of a physiological state in the cell or may be used to identify the potential toxicity of a compound, for instance a new or unknown compound or agent. The comparison of expression data, as well as available sequence or other information may be done by researcher or diagnostician or may be done with the aid of a computer and databases as described below.

In another format, the levels of a gene(s) of Tables 1-5, its encoded protein(s), or any metabolite produced by the encoded protein may be monitored or detected in a sample, such as a bodily tissue or fluid sample to identify or diagnose a physiological state of an organism. Such samples may include any tissue or fluid sample, including urine, blood and easily obtainable cells such as peripheral lymphocytes.

Use of the Markers for Monitoring Toxicity Progression

As described above, the genes and gene expression information provided in Tables 1-5 may also be used as markers for the monitoring of toxicity progression, such as that found after initial exposure to a drug, drug candidate, toxin, pollutant, etc. For instance, a tissue or cell sample may be assayed by any of the methods described above, and the expression levels from a gene or genes from Tables 1-5 may be compared to the expression levels found in tissue or cells exposed to the renal toxins described herein. The comparison of the expression data, as well as available sequence or other information may be done by a researcher or diagnostician or may be done with the aid of a computer and databases.

Use of the Toxicity Markers for Drug Screening

According to the present invention, the genes identified in Tables 1-5 may be used as markers or drug targets to evaluate the effects of a candidate drug, chemical compound or other agent on a cell or tissue sample. The genes may also be used as drug targets to screen for agents that modulate their expression and/or activity. In various formats, a candidate drug or agent can be screened for the ability to stimulate the transcription or expression of a given marker or markers or to down-regulate or counteract the transcription or expression of a marker or markers. According to the present invention, one can also compare the specificity of a drug's effects by looking at the number of markers which the drug induces and comparing them. More specific drugs will have less transcriptional targets. Similar sets of markers identified for two drugs may indicate a similarity of effects.

Assays to monitor the expression of a marker or markers as defined in Tables 1-5 may utilize any available means of monitoring for changes in the expression level of the nucleic acids of the invention. As used herein, an agent is said to modulate the expression of a nucleic acid of the invention if it is capable of up- or down-regulating expression of the nucleic acid in a cell.

In one assay format, gene chips containing probes to one, two or more genes from Tables 1-5 may be used to directly monitor or detect changes in gene expression in the treated or exposed cell. Cell lines, tissues or other samples are first exposed to a test agent and in some instances, a known toxin, and the detected expression levels of one or more, or preferably 2 or more of the genes of Tables 1-5 are compared to the expression levels of those same genes exposed to a known toxin alone. Compounds that modulate the expression patterns of the known toxin(s) would be expected to modulate potential toxic physiological effects in vivo. The genes in Tables 1-5 are particularly appropriate markers in these assays as they are differentially expressed in cells upon exposure to a known renal toxin. Tables 1 and 2 disclose those genes that are differentially expressed upon exposure to the named toxins and their corresponding GenBank Accession numbers. Table 3 discloses the human homologues and the corresponding GenBank Accession numbers of the differentially expressed genes of Tables 1 and 2.

In another format, cell lines that contain reporter gene fusions between the open reading frame and/or the transcriptional regulatory regions of a gene in Tables 1-5 and any assayable fusion partner may be prepared. Numerous assayable fusion partners are known and readily available including the firefly luciferase gene and the gene encoding chloramphenicol acetyltransferase (Alam et al. (1990), Anal Biochem 188: 245-254). Cell lines containing the reporter gene fusions are then exposed to the agent to be tested under appropriate conditions and time. Differential expression of the reporter gene between samples exposed to the agent and control samples identifies agents which modulate the expression of the nucleic acid.

Additional assay formats may be used to monitor the ability of the agent to modulate the expression of a gene identified in Tables 1-5. For instance, as described above, mRNA expression may be monitored directly by hybridization of probes to the nucleic acids of the invention. Cell lines are exposed to the agent to be tested under appropriate conditions and time, and total RNA or mRNA is isolated by standard procedures such those disclosed in Sambrook et al. (Molecular Cloning: A Laboratory Manual, 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989).

In another assay format, cells or cell lines are first identified which express the gene products of the invention physiologically. Cells and/or cell lines so identified would be expected to comprise the necessary cellular machinery such that the fidelity of modulation of the transcriptional apparatus is maintained with regard to exogenous contact of agent with appropriate surface transduction mechanisms and/or the cytosolic cascades. Further, such cells or cell lines may be transduced or transfected with an expression vehicle (e.g., a plasmid or viral vector) construct comprising an operable non-translated 5′-promoter containing end of the structural gene encoding the gene products of Tables 1-5 fused to one or more antigenic fragments or other detectable markers, which are peculiar to the instant gene products, wherein said fragments are under the transcriptional control of said promoter and are expressed as polypeptides whose molecular weight can be distinguished from the naturally occurring polypeptides or may further comprise an immunologically distinct or other detectable tag. Such a process is well known in the art (see Sambrook et al., supra).

Cells or cell lines transduced or transfected as outlined above are then contacted with agents under appropriate conditions; for example, the agent comprises a pharmaceutically acceptable excipient and is contacted with cells comprised in an aqueous physiological buffer such as phosphate buffered saline (PBS) at physiological pH, Eagles balanced salt solution (BSS) at physiological pH, PBS or BSS comprising serum or conditioned media comprising PBS or BSS and/or serum incubated at 37° C. Said conditions may be modulated as deemed necessary by one of skill in the art. Subsequent to contacting the cells with the agent, said cells are disrupted and the polypeptides of the lysate are fractionated such that a polypeptide fraction is pooled and contacted with an antibody to be further processed by immunological assay (e.g., ELISA, immunoprecipitation or Western blot). The pool of proteins isolated from the agent-contacted sample is then compared with the control samples (no exposure and exposure to a known toxin) where only the excipient is contacted with the cells and an increase or decrease in the immunologically generated signal from the agent-contacted sample compared to the control is used to distinguish the effectiveness and/or toxic effects of the agent.

Another embodiment of the present invention provides methods for identifying agents that modulate at least one activity of a protein(s) encoded by the genes in Tables 1-5. Such methods or assays may utilize any means of monitoring or detecting the desired activity.

In one format, the relative amounts of a protein (Tables 1-5) between a cell population that has been exposed to the agent to be tested compared to an un-exposed control cell population and a cell population exposed to a known toxin may be assayed. In this format, probes such as specific antibodies are used to monitor the differential expression of the protein in the different cell populations. Cell lines or populations are exposed to the agent to be tested under appropriate conditions and time. Cellular lysates may be prepared from the exposed cell line or population and a control, unexposed cell line or population. The cellular lysates are then analyzed with the probe, such as a specific antibody.

Agents that are assayed in the above methods can be randomly selected or rationally selected or designed. As used herein, an agent is said to be randomly selected when the agent is chosen randomly without considering the specific sequences involved in the association of a protein of the invention alone or with its associated substrates, binding partners, etc. An example of randomly selected agents is the use a chemical library or a peptide combinatorial library, or a growth broth of an organism.

As used herein, an agent is said to be rationally selected or designed when the agent is chosen on a nonrandom basis which takes into account the sequence of the target site and/or its conformation in connection with the agent's action. Agents can be rationally selected or rationally designed by utilizing the peptide sequences that make up these sites. For example, a rationally selected peptide agent can be a peptide whose amino acid sequence is identical to or a derivative of any functional consensus site.

The agents of the present invention can be, as examples, peptides, small molecules, vitamin derivatives, as well as carbohydrates. Dominant negative proteins, DNAs encoding these proteins, antibodies to these proteins, peptide fragments of these proteins or mimics of these proteins may be introduced into cells to affect function. “Mimic” used herein refers to the modification of a region or several regions of a peptide molecule to provide a structure chemically different from the parent peptide but topographically and functionally similar to the parent peptide (see G. A. Grant in: Molecular Biology and Biotechnology, Meyers, ed., pp. 659-664, VCH Publishers, New York, 1995). A skilled artisan can readily recognize that there is no limit as to the structural nature of the agents of the present invention.

Nucleic Acid Assay Formats

The genes identified as being differentially expressed upon exposure to a known renal toxin (Tables 1-5) may be used in a variety of nucleic acid detection assays to detect or quantify the expression level of a gene or multiple genes in a given sample. The genes described in Tables 1-5 may also be used in combination with one or more additional genes whose differential expression is associate with toxicity in a cell or tissue. In preferred embodiments, the genes in Tables 1-5 may be combined with one or more of the genes described in prior and related application Nos. 60/292,335; 60/297,523; 60/298,925; 60/303,810; 60/303,807; 60/303,808; 60/315,047; 60/324,928; 60/330,867; 60/330,462; 60/331,805; 60/336,144; 60/340,873; 60/357,843; 60/357,842; 60/357,844; 60/364,134; 60/370,206; 60/370,247; 60/370,144; 60/371,679; 60/372,794, 09/917,800 and 10/060,087 all of which are incorporated by reference on page 1 of this application.

Any assay format to detect gene expression may be used. For example, traditional Northern blotting, dot or slot blot, nuclease protection, primer directed amplification, RT-PCR, semi- or quantitative PCR, branched-chain DNA and differential display methods may be used for detecting gene expression levels. Those methods are useful for some embodiments of the invention. In cases where smaller numbers of genes are detected, amplification based assays may be most efficient. Methods and assays of the invention, however, may be most efficiently designed with hybridization-based methods for detecting the expression of a large number of genes.

Any hybridization assay format may be used, including solution-based and solid support-based assay formats. Solid supports containing oligonucleotide probes for differentially expressed genes of the invention can be filters, polyvinyl chloride dishes, particles, beads, microparticles or silicon or glass based chips, etc. Such chips, wafers and hybridization methods are widely available, for example, those disclosed by Beattie (WO 95/11755).

Any solid surface to which oligonucleotides can be bound, either directly or indirectly, either covalently or non-covalently, can be used. A preferred solid support is a high density array or DNA chip. These contain a particular oligonucleotide probe in a predetermined location on the array. Each predetermined location may contain more than one molecule of the probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There may be, for example, from 2, 10, 100, 1000 to 10,000, 100,000 or 400,000 or more of such features on a single solid support. The solid support, or the area within which the probes are attached may be on the order of about a square centimeter. Probes corresponding to the genes of Tables 1-5 or from the related applications described above may be attached to single or multiple solid support structures, e.g., the probes may be attached to a single chip or to multiple chips to comprise a chip set.

Oligonucleotide probe arrays for expression monitoring can be made and used according to any techniques known in the art (see for example, Lockhart et al (1996), Nat Biotechnol 14:1675-1680; McGall et al. (1996), Proc Nat Acad Sci USA 93:13555-13460). Such probe arrays may contain at least two or more oligonucleotides that are complementary to or hybridize to two or more of the genes described in Tables 1-5. For instance, such arrays may contain oligonucleotides that are complementary to or hybridize to at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 50, 70, 100 or more of the genes described herein. Preferred arrays contain all or nearly all of the genes listed in Tables 1-5, or individually, the gene sets of Tables 5-5CC. In a preferred embodiment, arrays are constructed that contain oligonucleotides to detect all or nearly all of the genes in any one of or all of Tables 1-5 on a single solid support substrate, such as a chip.

The sequences of the expression marker genes of Tables 1-5 are in the public databases. Table 1 provides the GenBank Accession Number or NCBI RefSeq ID for each of the sequences. Table 3 provides the LocusLink and Unigene names and descriptions for the human homologues of the genes described in Tables 1 and 2. The sequences of the genes in GenBank and/or RefSeq are expressly herein incorporated by reference in their entirety as of the filing date of this application, as are related sequences, for instance, sequences from the same gene of different lengths, variant sequences, polymorphic sequences, genomic sequences of the genes and related sequences from different species, including the human counterparts, where appropriate. These sequences may be used in the methods of the invention or may be used to produce the probes and arrays of the invention. In some embodiments, the genes in Tables 1-5 that correspond to the genes or fragments previously associated with a toxic response may be excluded from the Tables. p As described above, in addition to the sequences of the GenBank Accession Numbers or NCBI Refeq ID's disclosed in the Tables 1-5, sequences such as naturally occurring variants or polymorphic sequences may be used in the methods and compositions of the invention. For instance, expression levels of various allelic or homologous forms of a gene disclosed in Tables 1-5 may be assayed. Any and all nucleotide variations that do not alter the functional activity of a gene listed in the Tables 1-5, including all naturally occurring allelic variants of the genes herein disclosed, may be used in the methods and to make the compositions (e.g., arrays) of the invention.

Probes based on the sequences of the genes described above may be prepared by any commonly available method. Oligonucleotide probes for screening or assaying a tissue or cell sample are preferably of sufficient length to specifically hybridize only to appropriate, complementary genes or transcripts. Typically the oligonucleotide probes will be at least about 10, 12, 14, 16, 18, 20 or 25 nucleotides in length. In some cases, longer probes of at least 30, 40, or 50 nucleotides will be desirable.

As used herein, oligonucleotide sequences that are complementary to one or more of the genes described in Tables 1-5 refer to oligonucleotides that are capable of hybridizing under stringent conditions to at least part of the nucleotide sequences of said genes. Such hybridizable oligonucleotides will typically exhibit at least about 75% sequence identity at the nucleotide level to said genes, preferably about 80% or 85% sequence identity or more preferably about 90% or 95% or more sequence identity to said genes.

“Bind(s) substantially” refers to complementary hybridization between a probe nucleic acid and a target nucleic acid and embraces minor mismatches that can be accommodated by reducing the stringency of the hybridization media to achieve the desired detection of the target polynucleotide sequence.

The terms “background” or “background signal intensity” refer to hybridization signals resulting from non-specific binding, or other interactions, between the labeled target nucleic acids and components of the oligonucleotide array (e.g., the oligonucleotide probes, control probes, the array substrate, etc.). Background signals may also be produced by intrinsic fluorescence of the array components themselves. A single background signal can be calculated for the entire array, or a different background signal may be calculated for each target nucleic acid. In a preferred embodiment, background is calculated as the average hybridization signal intensity for the lowest 5% to 10% of the probes in the array, or, where a different background signal is calculated for each target gene, for the lowest 5% to 10% of the probes for each gene. Of course, one of skill in the art will appreciate that where the probes to a particular gene hybridize well and thus appear to be specifically binding to a target sequence, they should not be used in a background signal calculation. Alternatively, background may be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g. probes directed to nucleic acids of the opposite sense or to genes not found in the sample such as bacterial genes where the sample is mammalian nucleic acids). Background can also be calculated as the average signal intensity produced by regions of the array that lack any probes at all.

The phrase “hybridizing specifically to” or “specifically hybridizes” refers to the binding, duplexing, or hybridizing of a molecule substantially to or only to a particular nucleotide sequence or sequences under stringent conditions when that sequence is present in a complex mixture (e.g., total cellular) DNA or RNA.

Assays and methods of the invention may utilize available formats to simultaneously screen at least about 100, preferably about 1000, more preferably about 10,000 and most preferably about 1,000,000 different nucleic acid hybridizations.

As used herein a “probe” is defined as a nucleic acid, capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i.e., A, G, U, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in probes may be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.

The term “perfect match probe” refers to a probe that has a sequence that is perfectly complementary to a particular target sequence. The test probe is typically perfectly complementary to a portion (subsequence) of the target sequence. The perfect match (PM) probe can be a “test probe”, a “normalization control” probe, an expression level control probe and the like. A perfect match control or perfect match probe is, however, distinguished from a “mismatch control” or “mismatch probe.”

The terms “mismatch control” or “mismatch probe” refer to a probe whose sequence is deliberately selected not to be perfectly complementary to a particular target sequence. For each mismatch (MM) control in a high-density array there typically exists a corresponding perfect match (PM) probe that is perfectly complementary to the same particular target sequence. The mismatch may comprise one or more bases.

While the mismatch(es) may be located anywhere in the mismatch probe, terminal mismatches are less desirable as a terminal mismatch is less likely to prevent hybridization of the target sequence. In a particularly preferred embodiment, the mismatch is located at or near the center of the probe such that the mismatch is most likely to destabilize the duplex with the target sequence under the test hybridization conditions.

The term “stringent conditions” refers to conditions under which a probe will hybridize to its target subsequence, but with only insubstantial hybridization to other sequences or to other sequences such that the difference may be identified. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH.

Typically, stringent conditions will be those in which the salt concentration is at least about 0.01 to 1.0 M Na ⁺ ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.

The “percentage of sequence identity” or “sequence identity” is determined by comparing two optimally aligned sequences or subsequences over a comparison window or span, wherein the portion of the polynucleotide sequence in the comparison window may optionally comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical submit (e.g. nucleic acid base or amino acid residue) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Percentage sequence identity when calculated using the programs GAP or BESTFIT (see below) is calculated using default gap weights.

Probe Design

One of skill in the art will appreciate that an enormous number of array designs are suitable for the practice of this invention. The high density array will typically include a number of test probes that specifically hybridize to the sequences of interest. Probes may be produced from any region of the genes identified in the Tables and the attached representative sequence listing. In instances where the gene reference in the Tables is an EST, probes may be designed from that sequence or from other regions of the corresponding full-length transcript that may be available in any of the sequence databases, such as those herein described. See WO 99/32660 for methods of producing probes for a given gene or genes. In addition, any available software may be used to produce specific probe sequences, including, for instance, software available from Molecular Biology Insights, Olympus Optical Co. and Biosoft International. In a preferred embodiment, the array will also include one or more control probes.

High density array chips of the invention include “test probes.” Test probes may be oligonucleotides that range from about 5 to about 500, or about 7 to about 50 nucleotides, more preferably from about 10 to about 40 nucleotides and most preferably from about 15 to about 35 nucleotides in length. In other particularly preferred embodiments, the probes are 20 or 25 nucleotides in length. In another preferred embodiment, test probes are double or single strand DNA sequences such as cDNA fragments. DNA sequences are isolated or cloned from natural sources or amplified from natural sources using native nucleic acid as templates. These probes have sequences complementary to particular subsequences of the genes whose expression they are designed to detect. Thus, the test probes are capable of specifically hybridizing to the target nucleic acid they are to detect.

In addition to test probes that bind the target nucleic acid(s) of interest, the high density array can contain a number of control probes. The control probes may fall into three categories referred to herein as 1) normalization controls; 2) expression level controls; and 3) mismatch controls.

Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened. The signals obtained from the normalization controls after hybridization provide a control for variations in hybridization conditions, label intensity, “reading” efficiency and other factors that may cause the signal of a perfect hybridization to vary between arrays. In a preferred embodiment, signals (e.g., fluorescence intensity) read from all other probes in the array are divided by the signal (e.g., fluorescence intensity) from the control probes thereby normalizing the measurements.

Virtually any probe may serve as a normalization control. However, it is recognized that hybridization efficiency varies with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes present in the array, however, they can be selected to cover a range of lengths. The normalization control(s) can also be selected to reflect the (average) base composition of the other probes in the array, however in a preferred embodiment, only one or a few probes are used and they are selected such that they hybridize well (i.e., no secondary structure) and do not match any target-specific probes.

Expression level controls are probes that hybridize specifically with constitutively expressed genes in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level controls. Typically expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes” including, but not limited to the actin gene, the transferrin receptor gene, the GAPDH gene, and the like.

Mismatch controls may also be provided for the probes to the target genes, for expression level controls or for normalization controls. Mismatch controls are oligonucleotide probes or other nucleic acid probes identical to their corresponding test or control probes except for the presence of one or more mismatched bases. A mismatched base is a base selected so that it is not complementary to the corresponding base in the target sequence to which the probe would otherwise specifically hybridize. One or more mismatches are selected such that under appropriate hybridization conditions (e.g., stringent conditions) the test or control probe would be expected to hybridize with its target sequence, but the mismatch probe would not hybridize (or would hybridize to a significantly lesser extent). Preferred mismatch probes contain a central mismatch. Thus, for example, where a probe is a 20 mer, a corresponding mismatch probe will have the identical sequence except for a single base mismatch (e.g., substituting a G, a C or a T for an A) at any of positions 6 through 14 (the central mismatch).

Mismatch probes thus provide a control for non-specific binding or cross hybridization to a nucleic acid in the sample other than the target to which the probe is directed. For example, if the target is present the perfect match probes should be consistently brighter than the mismatch probes. In addition, if all central mismatches are present, the mismatch probes can be used to detect a mutation, for instance, a mutation of a gene in the accompanying Tables 1-5. The difference in intensity between the perfect match and the mismatch probe provides a good measure of the concentration of the hybridized material.

Nucleic Acid Samples

Cell or tissue samples may be exposed to the test agent in vitro or in vivo. When cultured cells or tissues are used, appropriate mammalian cell extracts, such as liver extracts, may also be added with the test agent to evaluate agents that may require biotransformation to exhibit toxicity. In a preferred format, primary isolates of animal or human renal cells which already express the appropriate complement of drug-metabolizing enzymes may be exposed to the test agent without the addition of mammalian kidney extracts.

The genes which are assayed according to the present invention are typically in the form of mRNA or reverse transcribed mRNA. The genes may or may not be cloned. The genes may or may not be amplified. The cloning and/or amplification do not appear to bias the representation of genes within a population. In some assays, it may be preferable, however, to use polyA+ RNA as a source, as it can be used with less processing steps.

As is apparent to one of ordinary skill in the art, nucleic acid samples used in the methods and assays of the invention may be prepared by any available method or process. Methods of isolating total mRNA are well known to those of skill in the art. For example, methods of isolation and purification of nucleic acids are described in detail in Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 24, Hybridization With Nucleic Acid Probes: Theory and Nucleic Acid Probes, P. Tijssen, Ed., Elsevier Press, New York, 1993. Such samples include RNA samples, but also include cDNA synthesized from a mRNA sample isolated from a cell or tissue of interest. Such samples also include DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. One of skill in the art would appreciate that it is desirable to inhibit or destroy RNase present in homogenates before homogenates are used.

Biological samples may be of any biological tissue or fluid or cells from any organism as well as cells raised in vitro, such as cell lines and tissue culture cells. Frequently the sample will be a tissue or cell sample that has been exposed to a compound, agent, drug, pharmaceutical composition, potential environmental pollutant or other composition. In some formats, the sample will be a “clinical sample” which is a sample derived from a patient. Typical clinical samples include, but are not limited to, sputum, blood, blood-cells (e.g., white cells), tissue or fine needle biopsy samples, urine, peritoneal fluid, and pleural fluid, or cells therefrom. Biological samples may also include sections of tissues, such as frozen sections or formalin fixed sections taken for histological purposes.

Forming High Density Arrays

Methods of forming high density arrays of oligonucleotides with a minimal number of synthetic steps are known. The oligonucleotide analogue array can be synthesized on a single or on multiple solid substrates by a variety of methods, including, but not limited to, light-directed chemical coupling, and mechanically directed coupling (see Pirrung, U.S. Pat. No. 5,143,854).

In brief, the light-directed combinatorial synthesis of oligonucleotide arrays on a glass surface proceeds using automated phosphoramidite chemistry and chip masking techniques. In one specific implementation, a glass surface is derivatized with a silane reagent containing a functional group, e.g., a hydroxyl or amine group blocked by a photolabile protecting group. Photolysis through a photolithographic mask is used selectively to expose functional groups which are then ready to react with incoming 5′ photoprotected nucleoside phosphoramidites. The phosphoramidites react only with those sites which are illuminated (and thus exposed by removal of the photolabile blocking group). Thus, the phosphoramidites only add to those areas selectively exposed from the preceding step. These steps are repeated until the desired array of sequences have been synthesized on the solid surface. Combinatorial synthesis of different oligonucleotide analogues at different locations on the array is determined by the pattern of illumination during synthesis and the order of addition of coupling reagents.

In addition to the foregoing, additional methods which can be used to generate an array of oligonucleotides on a single substrate are described in PCT Publication Nos. WO 93/09668 and WO 01/23614. High density nucleic acid arrays can also be fabricated by depositing pre-made or natural nucleic acids in predetermined positions. Synthesized or natural nucleic acids are deposited on specific locations of a substrate by light directed targeting and oligonucleotide directed targeting. Another embodiment uses a dispenser that moves from region to region to deposit nucleic acids in specific spots.

Hybridization

Nucleic acid hybridization simply involves contacting a probe and target nucleic acid under conditions where the probe and its complementary target can form stable hybrid duplexes through complementary base pairing. See WO 99/32660. The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. It is generally recognized that nucleic acids are denatured by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids. Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA, or RNA:DNA) will form even where the annealed sequences are not perfectly complementary. Thus, specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature or lower salt) successful hybridization tolerates fewer mismatches. One of skill in the art will appreciate that hybridization conditions may be selected to provide any degree of stringency.

In a preferred embodiment, hybridization is performed at low stringency, in this case in 6×SSPET at 37° C. (0.005% Triton X-100), to ensure hybridization and then subsequent washes are performed at higher stringency (e.g., 1×SSPET at 37° C.) to eliminate mismatched hybrid duplexes. Successive washes may be performed at increasingly higher stringency (e.g., down to as low as 0.25×SSPET at 37° C. to 50° C.) until a desired level of hybridization specificity is obtained. Stringency can also be increased by addition of agents such as formamide. Hybridization specificity may be evaluated by comparison of hybridization to the test probes with hybridization to the various controls that can be present (e.g., expression level control, normalization control, mismatch controls, etc.).

In general, there is a tradeoff between hybridization specificity (stringency) and signal intensity. Thus, in a preferred embodiment, the wash is performed at the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity. Thus, in a preferred embodiment, the hybridized array may be washed at successively higher stringency solutions and read between each wash. Analysis of the data sets thus produced will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.

Signal Detection

The hybridized nucleic acids are typically detected by detecting one or more labels attached to the sample nucleic acids. The labels may be incorporated by any of a number of means well known to those of skill in the art. See WO 99/32660.

Databases

The present invention includes relational databases containing sequence information, for instance, for the genes of Tables 1-5, as well as gene expression information from tissue or cells exposed to various standard toxins, such as those herein described (see Tables 5-5CC). Databases may also contain information associated with a given sequence or tissue sample such as descriptive information about the gene associated with the sequence information (see Tables 1 and 2), or descriptive information concerning the clinical status of the tissue sample, or the animal from which the sample was derived. The database may be designed to include different parts, for instance a sequence database and a gene expression database. Methods for the configuration and construction of such databases and computer-readable media to which such databases are saved are widely available, for instance, see U.S. Pat. No. 5,953,727, which is herein incorporated by reference in its entirety.

The databases of the invention may be linked to an outside or external database such as GenBank (www.ncbi.nlm.nih.gov/entrez.index.html); KEGG (www.genome.ad.jp/kegg); SPAD (www.grt.kuyshu-u.ac.jp/spad/index.html); HUGO (www.gene.ucl.ac.uk/hugo); Swiss-Prot (www.expasy.ch.sprot); Prosite (www.expasy.ch/tools/scnpsitl.html); OMIM (www.ncbi.nlm.nih.gov/omim); and GDB (www.gdb.org). In a preferred embodiment, as described in Tables 1-5, the external database is GenBank and the associated databases maintained by the National Center for Biotechnology Information (NCBI) (www.ncbi.nlm.nih.gov).

Any appropriate computer platform, user interface, etc. may be used to perform the necessary comparisons between sequence information, gene expression information and any other information in the database or information provided as an input. For example, a large number of computer workstations are available from a variety of manufacturers, such has those available from Silicon Graphics. Client/server environments, database servers and networks are also widely available and appropriate platforms for the databases of the invention.

The databases of the invention may be used to produce, among other things, electronic Northerns that allow the user to determine the cell type or tissue in which a given gene is expressed and to allow determination of the abundance or expression level of a given gene in a particular tissue or cell.

The databases of the invention may also be used to present information identifying the expression level in a tissue or cell of a set of genes comprising one or more of the genes in Tables 1-5, comprising the step of comparing the expression level of at least one gene in Tables 1-5 in a cell or tissue exposed to a test agent to the level of expression of the gene in the database. Such methods may be used to predict the toxic potential of a given compound by comparing the level of expression of a gene or genes in Tables 1-5 from a tissue or cell sample exposed to the test agent to the expression levels found in a control tissue or cell samples exposed to a standard toxin or renal toxin such as those herein described. Such methods may also be used in the drug or agent screening assays as described herein.

Kits

The invention further includes kits combining, in different combinations, high-density oligonucleotide arrays, reagents for use with the arrays, protein reagents encoded by the genes of the Tables, signal detection and array-processing instruments, gene expression databases and analysis and database management software described above. The kits may be used, for example, to predict or model the toxic response of a test compound, to monitor the progression of renal disease states, to identify genes that show promise as new drug targets and to screen known and newly designed drugs as discussed above.

The databases packaged with the kits are a compilation of expression patterns from human or laboratory animal genes and gene fragments (corresponding to the genes of Tables 1-5). In particular, the database software and packaged information that may contain the databases saved to a computer-readable medium include the expression results of Tables 1-5 that can be used to predict toxicity of a test agent by comparing the expression levels of the genes of Tables 1-5 induced by the test agent to the expression levels presented in Tables 5-5CC. In another format, database and software information may be provided in a remote electronic format, such as a website, the address of which may be packaged in the kit.

The kits may used in the pharmaceutical industry, where the need for early drug testing is strong due to the high costs associated with drug development, but where bioinformatics, in particular gene expression informatics, is still lacking. These kits will reduce the costs, time and risks associated with traditional new drug screening using cell cultures and laboratory animals. The results of large-scale drug screening of pre-grouped patient populations, pharmacogenomics testing, can also be applied to select drugs with greater efficacy and fewer side-effects. The kits may also be used by smaller biotechnology companies and research institutes who do not have the facilities for performing such large-scale testing themselves.

Databases and software designed for use with microarrays is discussed in Balaban et al., U.S. Pat. No. 6,229,911, a computer-implemented method for managing information, stored as indexed Tables 1-5, collected from small or large numbers of microarrays, and U.S. Pat. No. 6,185,561, a computer-based method with data mining capability for collecting gene expression level data, adding additional attributes and reformatting the data to produce answers to various queries. Chee et al., U.S. Pat. No. 5,974,164, disclose a software-based method for identifying mutations in a nucleic acid sequence based on differences in probe fluorescence intensities between wild type and mutant sequences that hybridize to reference sequences.

Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. The following working examples therefore, specifically point out the preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.

EXAMPLES

Example 1

Identification of Toxicity Markers

The renal toxins cephaloridine, cisplatin, puromycin aminonucleoside (PAN), bromoethylamine hydrobromide (BEA), gentamicin, ifosfamide, cyclophosphamide, carboplatin, AY-25329, indomethacin, acyclovir, citrin mercuric chloride, diflunisal, cidofovir, pamidronate, lithium, hydralazine, colchicine, sulfadiazine, and adriamycin and control compositions were administered to male Sprague-Dawley rats at various timepoints using administration diluents, protocols and dosing regimes as previously described in the art and previously described in the priority applications discussed above. The low and high dose level for each compound are provided in the chart below.

		High
		Dose	Method
Renal Toxin	Low Dose (mg/kg)	(mg/kg)	of Administration
cephaloridine	100	800	intravenous
cisplatin	1	5	intravenous
PAN	10	150	intravenous
BEA	10	200	intraperitoneal
gentamicin	2	80	intramuscular
ifosfamide	5	100	intraperitoneal
cyclophosphamide	20	2000	intraperitoneal
carboplatin	5	50	intravenous
AY-25329	25	250	oral gavage
indomethacin	1	10	oral gavage
acyclovir	10	100	intraperitoneal
citrinin	1	35	intraperitoneal
mercuric chloride	0.1	1	intravenous
diflunisal	2	400	oral gavage
cidofovir	10	100	intraperitoneal
pamidronate	1	60	intraperitoneal
lithium	0.3	3	intraperitoneal
	(nmol/kg)	(nmol/kg)
hydralazine	2.5	25	intraperitoneal
colchicine	0.15	1.5	intraperitoneal
sulfadiazine	100	1000	intravenous
adriamycin	1.3	12.8	intravenous

After administration, the dosed animals were observed and tissues were collected as described below:

Observation of Animals

1. Clinical Observations-	Twice daily: mortality and moribundity
	check. Cage Side Observations - skin and
	fur, eyes and mucous membrane, respiratory
	system, circulatory system, autonomic and
	central nervous system, somatomotor pattern,
	and behavior pattern.
	Potential signs of toxicity, including tremors,
	convulsions, salivation, diarrhea, lethargy,
	coma or other atypical behavior or
	appearance, were recorded as they occurred
	and included a time of onset, degree, and
	duration.
2. Physical Examinations-	Prior to randomization, prior to initial
	treatment, and prior to sacrifice.
3. Body Weights-	Prior to randomization, prior to initial
	treatment, and prior to sacrifice.

Clinical Pathology

1. Frequency	Prior to necropsy.
2. Number of animals	All surviving animals.
3. Bleeding Procedure	Blood was obtained by puncture of the orbital
	sinus while under 70% CO 2 /30% O 2 anesthesia.
4. Collection of	Approximately 0.5 mL of blood was
Blood Samples	collected into EDTA tubes for evaluation of
	hematology parameters. Approximately 1
	mL of blood was collected into serum
	separator tubes for clinical chemistry
	analysis. Approximately 200 uL of plasma
	was obtained and frozen at ~−80° C. for test
	compound/metabolite estimation. An
	additional ~2 mL of blood was collected into
	a 15 mL conical polypropylene vial to which
	~3 mL of Trizol was immediately added.
	The contents were immediately mixed with a
	vortex and by repeated inversion. The tubes
	were frozen in liquid nitrogen and stored at
	~−80° C.

Termination Procedures

Terminal Sacrifice

Approximately 3, 6, 24, 48, 72, 120, 144, 168, 336, and/or 360 hours after the initial dose, rats were weighed, physically examined, sacrificed by decapitation, and exsanguinated. The animals were necropsied within approximately five minutes of sacrifice. Separate sterile, disposable instruments were used for each animal, with the exception of bone cutters, which were used to open the skull cap. The bone cutters were dipped in disinfectant solution between animals.

Necropsies were conducted on each animal following procedures approved by board-certified pathologists.

Animals not surviving until terminal sacrifice were discarded without necropsy (following euthanasia by carbon dioxide asphyxiation, if moribund). The approximate time of death for moribund or found dead animals was recorded.

Postmortem Procedures

Fresh and sterile disposable instruments were used to collect tissues. Gloves were worn at all times when handling tissues or vials. All tissues were collected and frozen within approximately 5 minutes of the animal's death. The liver sections and kidneys were frozen within approximately 3-5 minutes of the animal's death. The time of euthanasia, an interim time point at freezing of liver sections and kidneys, and time at completion of necropsy were recorded. Tissues were stored at approximately −80° C. or preserved in 10% neutral buffered formalin.

Tissue Collection and Processing

• • Liver
  • 1. Right medial lobe—snap frozen in liquid nitrogen and stored at ˜−80° C.
  • 2. Left medial lobe—Preserved in 10% neutral-buffered formalin (NBF) and evaluated for gross and microscopic pathology.
  • 3. Left lateral lobe—snap frozen in liquid nitrogen and stored at ˜−80° C.
  • Heart
  • A sagittal cross-section containing portions of the two atria and of the two ventricles was preserved in 10% NBF. The remaining heart was frozen in liquid nitrogen and stored at ˜−80° C.
  • Kidneys (Both)
  • 1. Left—Hemi-dissected; half was preserved in 10% NBF and the remaining half was frozen in liquid nitrogen and stored at ˜−80° C.
  • 2. Right—Hemi-dissected; half was preserved in 10% NBF and the remaining half was frozen in liquid nitrogen and stored at ˜−80° C.
  • Testes (Both)
  • A sagittal cross-section of each testis was preserved in 10% NBF. The remaining testes were frozen together in liquid nitrogen and stored at ˜80° C.
  • Brain (Whole)
  • A cross-section of the cerebral hemispheres and of the diencephalon was preserved in 10% NBF, and the rest of the brain was frozen in liquid nitrogen and stored at ˜−80° C.

Microarray sample preparation was conducted with minor modifications, following the protocols set forth in the Affymetrix GeneChip Expression Analysis Manual. Frozen tissue was ground to a powder using a Spex Certiprep 6800 Freezer Mill. Total RNA was extracted with Trizol (GibcoBRL) utilizing the manufacturer's protocol. The total RNA yield for each sample was 200-500 μg per 300 mg tissue weight. mRNA was isolated using the Oligotex mRNA Midi kit (Qiagen) followed by ethanol precipitation. Double stranded cDNA was generated from mRNA using the SuperScript Choice system (GibcoBRL). First strand cDNA synthesis was primed with a T7-(dT24) oligonucleotide. The cDNA was phenol-chloroform extracted and ethanol precipitated to a final concentration of 1 μg/ml. From 2 μg of cDNA, cRNA was synthesized using Ambion's T7 MegaScript in vitro Transcription Kit.

To biotin label the cRNA, nucleotides Bio-11-CTP and Bio-16-UTP (Enzo Diagnostics) were added to the reaction. Following a 37° C. incubation for six hours, impurities were removed from the labeled cRNA following the RNeasy Mini kit protocol (Qiagen). cRNA was fragmented (fragmentation buffer consisting of 200 mM Tris-acetate, pH 8.1, 500 mM KOAc, 150 mM MgOAc) for thirty-five minutes at 94° C. Following the Affymetrix protocol, 55 μg of fragmented cRNA was hybridized on the Affymetrix rat array set for twenty-four hours at 60 rpm in a 45° C. hybridization oven. The chips were washed and stained with Streptavidin Phycoerythrin (SAPE) (Molecular Probes) in Affymetrix fluidics stations. To amplify staining, SAPE solution was added twice with an anti-streptavidin biotinylated antibody (Vector Laboratories) staining step in between. Hybridization to the probe arrays was detected by fluorometric scanning (Hewlett Packard Gene Array Scanner). Data was analyzed using Affymetrix GeneChip® version 2.0 and Expression Data Mining (EDMT) software (version 1.0), GeneExpress2000, and S-Plus.

Tables 1 and 2 disclose those genes that are differentially expressed upon exposure to the named toxins and their corresponding GenBank Accession and Sequence Identification numbers, the identities of the metabolic pathways in which the genes function, the gene names if known, and the unigene cluster titles. The model code represents the various toxicity state that each gene is able to discriminate as well as the individual toxin type associated with each gene. The codes are defined in Table 4. The GLGC ID is the internal Gene Logic identification number.

Table 3 discloses those genes that are the human homologues of those genes in Tables 1 and 2 that are differentially expressed upon exposure to the named toxins. The corresponding GenBank Accession and Sequence Identification numbers, the gene names if known, and the unigene cluster titles of the human homologues are listed.

Table 4 defines the comparison codes used in Tables 1, 2, 3, and 5.

Tables 5-5CC disclose the summary statistics for each of the comparisons performed. Each of these tables contains a set of predictive genes and creates a model for predicting the renal toxicity of an unknown, i.e., untested compound. Each gene is identified by its Gene Logic identification number and can be cross-referenced to a gene name and representative SEQ ID NO. in Tables 1 and 2. For each comparison of gene expression levels between samples in the toxicity group (samples affected by exposure to a specific toxin) and samples in the non-toxicity group (samples not affected by exposure to that same specific toxin), the tox mean (for toxicity group samples) is the mean signal intensity, as normalized for the various chip parameters that are being assayed. The non-tox mean represents the mean signal intensity, as normalized for the various chip parameters that are being assayed, in samples from animals other than those treated with the high dose of the specific toxin. These animals were treated with a low dose of the specific toxin, or with vehicle alone, or with a different toxin. Samples in the toxicity groups were obtained from animals sacrificed at the timepoint(s) indicated in the Table 5 headings, while samples in the non-toxicity groups were obtained from animals sacrificed at all time points in the experiments. For individual genes, an increase in the tox mean compared to the non-tox mean indicates up-regulation upon exposure to a toxin. Conversely, a decrease in the tox mean compared to the non-tox mean indicates down-regulation.

The mean values are derived from Average Difference (AveDiff) values for a particular gene, averaged across the corresponding samples. Each individual Average Difference value is calculated by integrating the intensity information from multiple probe pairs that are tiled for a particular fragment. The normalization multiplies each expression intensity for a given experiment (chip) by a global scaling factor. The intent of this normalization is to make comparisons of individual genes between chips possible. The scaling factor is calculated as follows:

1. From all the unnormalized expression values in the experiment, delete the largest 2% and smallest 2% of the values. That is, if the experiment yields 10,000 expression values, order the values and delete the smallest 200 and the largest 200.

2. Compute the trimmed mean, which is equal to the mean of the remaining values.

3. Compute the scale factor SF=100/(trimmed mean).

The value of 100 used here is the standard target value used. Some AveDiff values may be negative due to the general noise involved in nucleic acid hybridization experiments. Although many conclusions can be made corresponding to a negative value on the GeneChip platform, it is difficult to assess the meaning behind the negative value for individual fragments. Our observations show that, although negative values are observed at times within the predictive gene set, these values reflect a real biological phenomenon that is highly reproducible across all the samples from which the measurement was taken. For this reason, those genes that exhibit a negative value are included in the predictive set. It should be noted that other platforms of gene expression measurement may be able to resolve the negative numbers for the corresponding genes. The predictive ability of each of those genes should extend across platforms, however. Each mean value is accompanied by the standard deviation for the mean. The linear discriminant analysis score (discriminant score), as disclosed in the tables, measures the ability of each gene to predict whether or not a sample is toxic. The discriminant score is calculated by the following steps:

Calculation of a Discriminant Score

Let X _i represent the AveDiff values for a given gene across the non-tox samples, i=1 . . . n.

Let Y _i represent the AveDiff values for a given gene across the tox samples, i=1 . . . t.

The calculations proceed as follows:

1. Calculate mean and standard deviation for X _i 's and Y _i 's, and denote these by m _X , m _Y , s _X , s _Y .

2. For all X _i 's and Y _i 's, evaluate the function f(z)=((1/s _Y )*exp(−0.5*((z−m _Y )/s _Y ) ² ))/(((1/s _Y )*exp(−0.5*((z−m _Y )/s _Y ) ² ))+((1/s _X )*exp(−0.5*((z−m _X )/s _X ) ² ))).

3. The number of correct predictions, say P, is then the number of Y _i 's such that f(Y _i )>0.5 plus the number of X _i 's such that f(X _i )<0.5.

4. The discriminant score is then P/(n+t).

Linear discriminant analysis uses both the individual measurements of each gene and the calculated measurements of all combinations of genes to classify samples. For each gene a weight is derived from the mean and standard deviation of the toxic and nontox groups. Every gene is multiplied by a weight and the sum of these values results in a collective discriminate score. This discriminant score is then compared against collective centroids of the tox and nontox groups. These centroids are the average of all tox and nontox samples respectively. Therefore, each gene contributes to the overall prediction. This contribution is dependent on weights that are large positive or negative numbers if the relative distances between the tox and nontox samples for that gene are large and small numbers if the relative distances are small. The discriminant score for each unknown sample and centroid values can be used to calculate a probability between zero and one as to the group in which the unknown sample belongs.

Example 2

General Toxicity Modeling

Samples were selected for grouping into tox-responding and non-tox-responding groups by examining each study individually with Principal Components Analysis (PCA) to determine which treatments had an observable response. Only groups where confidence of their tox-responding and non-tox-responding status was established were included in building a general tox model (Table 5).

Linear discriminant models were generated to describe toxic and non-toxic samples. The top discriminant genes and/or EST's were used to determine toxicity by calculating each gene's contribution with homo and heteroscedastic treatment of variance and inclusion or exclusion of mutual information between genes. Prediction of samples within the database exceeded 80% true positives with a false positive rate of less than 5%. It was determined that combinations of genes and/or EST's generally provided a better predictive ability than individual genes and that the more genes and/or EST used the better predictive ability. Although the preferred embodiment includes fifty or more genes, many pairings or greater combinations of genes and/or EST can work better than individual genes. All combinations of two or more genes from the selected list (Table 5) could be used to predict toxicity. These combinations could be selected by pairing in an agglomerate, divisive, or random approach. Further, as yet undetermined genes and/or EST's could be combined with individual or combination of genes and/or EST's described here to increase predictive ability. However, the genes and/or EST's described here would contribute most of the predictive ability of any such undetermined combinations.

Other variations on the above method can provide adequate predictive ability. These include selective inclusion of components via agglomerate, divisive, or random approaches or extraction of loading and combining them in agglomerate, divisive, or random approaches. Also the use of composite variables in logistic regression to determine classification of samples can also be accomplished with linear discriminate analysis, neural or Bayesian networks, or other forms of regression and classification based on categorical or continual dependent and independent variables.

Example 3

Modeling Methods

The above modeling methods provide broad approaches of combining the expression of genes to predict sample toxicity. One could also provide no weight in a simple voting method or determine weights in a supervised or unsupervised method using agglomerate, divisive, or random approaches. All or selected combinations of genes may be combined in ordered, agglomerate, or divisive, supervised or unsupervised clustering algorithms with unknown samples for classification. Any form of correlation matrix may also be used to classify unknown samples. The spread of the group distribution and discriminate score alone provide enough information to enable a skilled person to generate all of the above types of models with accuracy that can exceed discriminate ability of individual genes. Some examples of methods that could be used individually or in combination after transformation of data types include but are not limited to: Discriminant Analysis, Multiple Discriminant Analysis, logistic regression, multiple regression analysis, linear regression analysis, conjoint analysis, canonical correlation, hierarchical cluster analysis, k-means cluster analysis, self-organizing maps, multidimensional scaling, structural equation modeling, support vector machine determined boundaries, factor analysis, neural networks, bayesian classifications, and resampling methods.

Example 4

Grouping of Individual Compound and Pathology Classes

Samples were grouped into individual pathology classes based on known toxicological responses and observed clinical chemical and pathology measurements or into early and late phases of observable toxicity within a compound (Tables 5A-3CC). The top 10, 25, 50, 100 genes based on individual discriminate scores were used in a model to ensure that combination of genes provided a better prediction than individual genes. As described above, all combinations of two or more genes from this list could potentially provide better prediction than individual genes when selected in any order or by ordered, agglomerate, divisive, or random approaches. In addition, combining these genes with other genes could provide better predictive ability, but most of this predictive ability would come from the genes listed herein.

Samples may be considered toxic if they score positive in any pathological or individual compound class represented here or in any modeling method mentioned under general toxicology models based on combination of individual time and dose grouping of individual toxic compounds obtainable from the data. The pathological groupings and early and late phase models are preferred examples of all obtainable combinations of sample time and dose points. Most logical groupings with one or more genes and one or more sample dose and time points should produce better predictions of general toxicity, pathological specific toxicity, or similarity to known toxicant than individual genes.

Although the present invention has been described in detail with reference to examples above, it is understood that various modifications can be made without departing from the spirit of the invention. Accordingly, the invention is limited only by the following claims. All cited patents, patent applications and publications referred to in this application are herein incorporated by reference in their entirety.

TABLE 1
SUMMARY
Sequence		GenBank Acc/	Model
ID No.	Identifier	Ref. Seq ID	Code	Gene Name	Unigene Cluster Title
1	6949	AA012785	q		ESTs
2	25098	AA108277	h, v
3	17312	AA108308	r		ESTs, Highly similar to includes exons
					3 through 12 [ M. musculus ]
4	16882	AA684537	o		ESTs, Moderately similar to NADH-
					ubiquinone oxidoreductase subunit CI-
					SGDH [ H. sapiens ]
5	6049	AA685178	y		ESTs, Highly similar to alpha
					NAC/1.9.2. protein [ M. musculus ]
6	4426	AA685974	l, m		ESTs
7	21815	AA686423	g		ESTs, Weakly similar to T23657
					hypothetical protein M01F1.6 -
					Caenorhabditis elegans [ C. elegans ]
8	1600	AA686470	i	DNA-damage inducible	DNA-damage inducible transcript 3
				transcript 3
8	1599	AA686470	i	DNA-damage inducible	DNA-damage inducible transcript 3
				transcript 3
9	21997	AA799325	u		ESTs
10	18396	AA799330	v		ESTs, Highly similar to AF132951 1
					CGI-17 protein [ H. sapiens ]
11	6581	AA799412	f, l		ESTs, Weakly similar to ESR1 RAT
					ESTROGEN RECEPTOR
					[ R. norvegicus ]
12	16538	AA799449	k		ESTs, Weakly similar to nucleosome
					assembly protein [ R. norvegicus ]
13	23294	AA799472	u		ESTs, Moderately similar to CGI-116
					protein [ H. sapiens ]
14	18290	AA799497	r		ESTs
15	18981	AA799523	e		ESTs, Moderately similar to hnRNP
					protein [ R. norvegicus ]
16	20843	AA799545	h		ESTs, Weakly similar to TCPA RAT T-
					COMPLEX PROTEIN 1, ALPHA
					SUBUNIT [ R. norvegicus ]
17	16993	AA799560	b		ESTs
18	16576	AA799570	d		ESTs
19	18361	AA799591	i		ESTs, Highly similar to TBB1 RAT
					TUBULIN BETA CHAIN
					[ R. norvegicus ]
20	17712	AA799598	z		ESTs
22	18346	AA799718	f		ESTs
23	8768	AA799726	l		ESTs
24	11687	AA799732	w		ESTs, Highly similar to Dgcr6 protein
					[ M. musculus ]
25	18349	AA799744	u		ESTs
26	17494	AA799751	n		ESTs
27	18360	AA799771	General		ESTs
28	18880	AA799801	w		ESTs
29	20998	AA799803	z		ESTs, Weakly similar to serine
					protease [ R. norvegicus ]
30	21006	AA799861	c		ESTs, Highly similar to IRF7 MOUSE
					INTERFERON REGULATORY
					FACTOR 7 [ M. musculus ]
31	15011	AA799893	General		ESTs, Highly similar to DDRT helix-
					destabilizing protein - rat
					[ R. norvegicus ]
32	20811	AA799899	a		ESTs, Highly similar to 60S
					RIBOSOMAL PROTEIN L18A
					[ R. norvegicus ]
33	23202	AA799971	General		ESTs, Weakly similar S52675
					probable membrane protein YDR109c
					yeast ( Saccharomyces cerevisiae )
					[ S. cerevisiae ]
34	4832	AA800190	b		ESTs, Highly similar to glycogen
					phosphorylase [ R. norvegicus ]
35	21656	AA800202	d		ESTs
36	18433	AA800218	j, y, z		ESTs, Weakly similar to T15476
					hypothetical protein C09F5.2 -
					Caenorhabditis elegans [ C. elegans ]
37	6386	AA800235	u		ESTs
38	18442	AA800258	h, k		ESTs
39	21092	AA800380	y		ESTs, Weakly similar to
					CORTICOSTEROID 11-BETA-
					DEHYDROGENASE, ISOZYME 1
					[ R. norvegicus ]
40	17325	AA800587	General		ESTs, Weakly similar to glutathione
					peroxidase [ R. norvegicus ]
41	13930	AA800613	cc,		Rattus norvegicus gene for TIS11,
			General		complete cds
42	21372	AA800693	v		ESTs
42	21373	AA800693	s		ESTs
43	18161	AA800701	k		ESTs
44	6595	AA800753	w		ESTs
45	13348	AA800928	General		ESTs
46	23115	AA801165	o, y		ESTs, Highly similar to H2A1 RAT
					HISTONE H2A.1 [ R. norvegicus ]
47	12399	AA801307	General		ESTs
48	7543	AA801395	General		ESTs
49	24237	AA817726	t, General		ESTs
50	11215	AA817921	o		ESTs, Moderately similar to T25763
					hypothetical protein F46F11.4 -
					Caenorhabditis elegans [ C. elegans ]
51	5985	AA818005	g		ESTs
52	11338	AA818016	x		ESTs, Highly similar to rabkinesin-6
					[ M. musculus ]
53	2845	AA818026	k, General		ESTs, Weakly similar to PRSC
					MOUSE 26S PROTEASOME
					REGULATORY SUBUNIT S12
					[ M. musculus ]
54	16756	AA818089	i, k,		ESTs, Highly similar to glycyl-tRNA
			General		synthetase [ H. sapiens ]
55	17771	AA818224	e, g, p,		ESTs, Highly similar to TBB1 RAT
			General		TUBULIN BETA CHAIN
					[ R. norvegicus ]
56	6522	AA818261	g, m		ESTs, Moderately similar to
					autoantigen p542 [ H. sapiens ]
57	5924	AA818359	y		ESTs
58	7806	AA818421	b, aa		ESTs
59	8237	AA818512	v		ESTs
60	17434	AA818574	h		ESTs
61	8728	AA818615	General		ESTs
62	6054	AA818658	b, v, cc,	Diphtheria toxin receptor	Diphtheria toxin receptor (heparin
			General	(heparin binding epidermal	binding epidermal growth factor - like
				growth factor - like growth	growth factor)
				factor)
63	11590	AA818721	d		ESTs, Moderately similar to S65785
					mel-13a protein - mouse [ M. musculus ]
64	4291	AA818741	q, General		ESTs
65	4330	AA818747	o, General		ESTs
66	19723	AA818761	v, General		ESTs
67	13684	AA818770	h, j, l, m		Rattus norvegicus serine protease
					gene, complete cds
68	6322	AA818801	k		ESTs
69	7690	AA818875	General	uroguanylin	uroguanylin
70	4952	AA818907	q, General		ESTs
71	6094	AA818911	t		ESTs
72	10985	AA818998	o, General		ESTs, Weakly similar to HP33
					[ R. norvegicus ]
73	6120	AA819008	t		ESTs
74	2586	AA819081	c		ESTs, Weakly similar testis specific
					protein [ R. norvegicus ]
76	6438	AA819269	o		ESTs
77	24721	AA819306	d, w		ESTs
78	6250	AA819376	o, y		Rattus norvegicus mRNA for inositol
					hexakisphosphate kinase, complete
					cds
80	6281	AA819517	j		ESTs, Weakly similar to JC5707
					HYA22 protein [ H. sapiens ]
81	10141	AA819526	j		ESTs
82	6551	AA819558	t		ESTs
83	6723	AA819653	r		ESTs, Moderately similar to dJ30M3.1
					[ H. sapines ]
84	14958	AA819744	aa		ESTs
85	19433	AA819776	v		ESTs, Weakly similar to HS9B RAT
					HEAT SHOCK PROTEIN HSP 90-
					BETA [ R. norvegicus ]
86	6204	AA819889	aa		ESTs
87	22820	AA848315	General	HMm: inosine 5′-phosphate	ESTs, Weakly similar to guanosine
				dehydrogenase 2	monophosphate reductase
					[ R. norvegicus ]
88	6614	AA848389	bb		ESTs, Weakly similar to T26686
					hypothetical protein Y38F1A.6 -
					Caenorhabditis elegans [ C. elegans ]
89	21125	M848437	General		ESTs
90	23504	M848496	q		ESTs, Moderately similar to
					IF4B_HUMAN EUKARYOTIC
					TRANSLATION INITIATION FACTOR
					4B [ H. sapiens ]
91	18532	AA848675	g		ESTs, Weakly similar to FMO1 RAT
					DIMETHYLANILINE
					MONOOXYGENASE [ R. norvegicus ]
92	21140	AA848738	c		ESTs
93	16128	AA848807	o		ESTs, Moderately similar to AF132946
					1 CGI-12 protein [ H. sapiens ]
94	22923	AA848929	g		ESTs
95	17339	AA849497	General		ESTs
96	11727	AA849518	l		ESTs
97	21275	AA849796	i, l, m,		ESTs
			General
98	16678	AA849827	aa		ESTs
99	8515	AA849917	e		ESTs
100	18447	AA849939	General		ESTs
101	12130	AA850037	p		ESTs
102	23981	AA850040	x, aa	cyclase-associated protein	cyclase-associated protein homologue
				homologue
103	13615	AA850364	t		ESTs, Moderately similar to RB17
					MOUSE RAS-RELATED PROTEIN
					RAB-17 [ M. musculus ]
105	2637	AA850893	x		ESTs, Highly similar to hypothetical
					protein [ H. sapiens ]
106	22093	AA850909	d		ESTs
107	21766	AA850916	c		ESTs
108	2847	AA850919	w		ESTs, Weakly similar to dithiolethione-
					inducible gene-1 [ R. norvegicus ]
109	12162	AA850975	h		Rattus norvegicus mRNA for ras-
					GTPase-activating protein SH3-
					domain binding protein, partial cds
110	9514	AA850978	General		ESTs
111	3924	AA851017	e, q		ESTs, Highly similar to molybdopterin-
					synthase large subunit [ M. musculus ]
111	3925	AA851017	o, General		ESTs, Highly similar to molybdopterin-
					synthase large subunit [ M. musculus ]
112	4490	AA851184	a, k		Rattus norvegicus mRNA for
					cathepsin Y, partial cds
113	19187	AA851230	General		ESTs, Weakly similar to T28050
					hypothetical protein ZK856.11 -
					Caenorhabditis elegans [ C. elegans ]
114	19189	AA851237	c		ESTs, Highly similar to ubiquitin
					specific protease UBP43
					[ M. musculus ]
115	15386	AA851241	m		ESTs, Highly similar to hypothetical
					protein [ H. sapiens ]
116	21462	AA851261	g, l,		ESTs, Weakly similar to A61382
			General		phosphorylation regulatory protein HP-
					10 [ H. sapiens ]
117	21471	AA851343	General		ESTs
118	16902	AA851379	p	HHs: NADH dehydrogenase	ESTs, Moderately similar to
				(ubiquinone) Fe—S protein 8	NUIM_HUMAN NADH-UBIQUINONE
				(23 kD) (NADH-coenzyme Q	OXIDOREDUCTASE 23 KD SUBUNIT
				reductase)	PRECURSOR [ H. sapiens ]
119	23376	AA851392	i, x		ESTs, Moderately similar to kinesin-
					like DNA binding protein [ H. sapiens ]
119	23377	AA851392	x		ESTs, Moderately similar to kinesin-
					like DNA binding protein [ H. sapiens ]
120	13349	AA851417	General		ESTs
121	21527	AA851733	r, u		ESTs
122	4048	AA851814	i, o, u,		Rattus norvegicus osteoactivin mRNA,
			General		complete cds
123	10561	AA851871	bb		ESTs, Highly similar to SSRA HUMAN
					TRANSLOCON-ASSOCIATED
					PROTEIN, ALPHA SUBUNIT
					PRECURSOR [ H. sapiens ]
124	17411	AA858621	j, y		Rattus norvegicus CaM-kinase II
					inhibitor alpha mRNA, complete cds
125	1801	AA858636	k, s, x, bb		ESTs, Weakly similar to MCM6 RAT
					DNA REPLICATION LICENSING
					FACTOR MCM6 [ R. norvegicus ]
126	18350	AA858674	p		ESTs
127	19484	AA858693	e		ESTs
128	6360	AA858696	d		ESTs
129	17334	AA858704	p		ESTs, Weakly similar to Reg receptor
					[ R. norvegicus ]
130	6380	AA858758	q		ESTs, Weakly similar to dJ413H6.1.1
					[ H. sapiens ]
131	13219	AA858759	a		ESTs
132	6384	AA858788	l, m, General		ESTs
134	13412	AA858830	p		ESTs, Highly similar to p40 seven-
					transmembrane-domain protein
					[ M. musculus ]
135	7279	AA858892	f		ESTs
136	18217	AA858930	t		ESTs
137	5867	AA858953	v, General	HHs: asparaginyl-tRNA	ASPARAGINYL-TRNA
				synthetase	SYNTHETASE, CYTOPLASMIC
					[ H. sapiens ]
138	14479	AA858969	r		ESTs, Moderately similar I56526
					interleukin 1 receptor type I - rat
					[ R. norvegicus ]
139	6431	AA859085	t		ESTs
140	17361	AA859114	o, General		ESTs
141	21025	AA859241	General	outer membrane protein	outer membrane protein
142	10076	AA859271	c		ESTs
143	21791	AA859333	k		ESTs, Weakly similar to CYSR RAT
					CYSTEINE-RICH PROTEIN 1
					[ R. norvegicus ]
144	16314	AA859348	cc, General		ESTs
145	18862	AA859520	f		ESTs
146	15059	AA859545	r		ESTs
147	19894	AA859581	s		Rattus norvegicus late gestation lung
					protein 1 (Lgl1) mRNA, complete cds
148	14353	AA859585	h		ESTs
149	16318	AA859648	h		ESTs, Weakly similar to DnaJ
					homolog 2 [ R. norvegicus ]
150	17316	AA859652	General		ESTs
151	19067	AA859663	n, q		ESTs
152	22406	AA859680	n		ESTs
153	20599	AA859690	x		ESTs
154	14261	AA859693	u		ESTs, Weakly similar to
					YNH2_CAEEL HYPOTHETICAL 31.0 KD
					PROTEIN R107.2 IN
					CHROMOSOME III [ C. elegans ]
155	14138	AA859700	v	HHs: protoporphyrinogen	ESTs, Highly similar to PPOX MOUSE
				oxidase	PROTOPORPHYRINOGEN OXIDASE
					[ M. musculus ]
155	14139	AA859700	v	HHs: protoporphyrinogen	ESTs, Highly similar to PPOX MOUSE
				oxidase	PROTOPORPHYRINOGEN OXIDASE
					[ M. musculus ]
157	22374	AA859804	l		ESTs, Weakly similar to IF4E MOUSE
					EUKARYOTIC TRANSLATION
					INITIATION FACTOR 4E
					[ R. norvegicus ]
158	22385	AA859805	b, k		ESTs, Moderately similar to LYOX
					RAT PROTEIN-LYSINE 6-OXIDASE
					PRECURSOR [ R. norvegicus ]
159	22773	AA859885	n		ESTs
160	22816	AA859898	k, x, z		ESTs
161	11891	AA859926	x		ESTs
162	23070	AA859942	k		ESTs, Highly similar to N-
					myristoyltransferase 1 [ M. musculus ]
163	23121	AA859948	k		ESTs
164	23166	AA859954	cc, General		ESTs
165	18468	AA859966	aa		ESTs, Weakly similar to Edp1 protein
					[ M. musculus ]
166	23336	AA859981	q	HHs: inosital(myo)-1(or 4)-	MYO-INOSITOL-1(OR 4)-
				monophosphatase 2	MONOPHOSPHATASE
					[ R. norvegicus ]
167	4222	AA860024	a, bb		ESTs, Highly similar to
					EF1G_HUMAN ELONGATION
					FACTOR 1-GAMMA [ H. sapiens ]
168	13974	AA860030	u, x, General		Rattus norvegicus mRNA for class I
					beta-tubulin, complete cds
169	7090	AA860039	x	Hyaluronan mediated motility	EST, Hyaluronan mediated motility
				receptor (RHAMM)	receptor (RHAMM)
170	23769	AA860055	k, x		ESTs, Moderately similar to T08661
					anti-silencing protein ASF1 homolog
					DKFZp547E2110.1 [ H. sapiens ]
171	16323	AA866240	w		EST
172	4462	AA866264	General		ESTs, Weakly similar to PE2R RAT 20
					ALPHA-HYDROXYSTEROID
					DEHYDROGENASE [ R. norvegicus ]
173	15884	AA866276	k		ESTs, Weakly similar to A60543
					protein kinase [ R. norvegicus ]
174	17742	AA866302	c, y	4-hydroxyphenylpyruvic acid	4-hydroxyphenylpyruvic acid
				dioxygenase	dioxygenase
175	16333	AA866414	a, h	Solute carrier family 4,	Solute carrier family 4, member 1,
				member 1, anion exchange	anion exchange protein 1 (kidney
				protein 1 (kidney band 3)	band 3)
176	18918	AA866444	p, q		ESTs, Moderately similar to AF141884
					1 oligophrenin-1 like protein
					[ H. sapiens ]
177	16853	AA866454	j, l, m, y, z		ESTs
178	18995	AA866459	h, m		ESTs
179	16013	AA866482	s		ESTs, Highly similar to FGD1 MOUSE
					PUTATIVE RHO/RAC GUANINE
					NUCLEOTIDE EXCHANGE FACTOR
					[ M. musculus ]
180	26036	AA874849	r
181	16059	AA874857	h		ESTs
182	16069	AA874873	r		ESTs
183	21633	AA874951	f		ESTs, Weakly similar to RNA binding
					protein [ H. sapiens ]
184	16192	AA874995	w		ESTs
185	16254	AA875025	j		ESTs, Highly similar to RET3 BOVIN
					RETINOIC ACID-BINDING PROTEIN
					I, CELLULAR [ R. norvegicus ]
186	16312	AA875032	cc, General		ESTs
187	20701	AA875097	b		Rat alpha-fibrinogen mRNA, 3′ end
188	16416	AA875098	bb		ESTs, Highly similar to ARF3_HUMAN
					ADP-RIBOSYLATION FACTOR
					[ R. norvegicus ]
189	16419	AA875102	bb		ESTs, Highly similar to
					RUXE_HUMAN SMALL NUCLEAR
					RIBONUCLEOPROTEIN E
					[ M. musculus ]
190	15313	AA875126	l, m,		ESTs
			General
191	10936	AA875146	w		ESTs, Weakly similar to AF151834 1
					CGI-76 protein [ H. sapiens ]
192	18084	AA875186	h		ESTs
193	15371	AA875205	u		ESTs, Highly similar to IF39_HUMAN
					EUKARYOTIC TRANSLATION
					INITIATION FACTOR 3 SUBUNIT 9
					[ H. sapiens ]
194	15401	AA875257	x, z		ESTs
195	15410	AA875268	p, s	HHs: NADH dehydrogenase	ESTs, Highly similar to NUKM
				(ubiquinone) Fe—S protein 7	HUMAN, partial CDS [ H. sapiens ]
				(20 kD) (NADH-coenzyme Q
				reductase)
196	15420	AA875286	f		ESTs
197	15446	AA875327	s, w		ESTs
198	7936	AA875495	b, General		ESTs
199	17314	AA875509	i, l, m		ESTs, Highly similar to includes exons
					3 through 12 [ M. musculus ]
200	24472	AA875523	k		ESTs, Highly similar to MLES RAT
					MYOSIN LIGHT CHAIN ALKALI,
					SMOOTH-MUSCLE ISOFORM
					[ R. norvegicus ]
201	15587	AA875577	j		ESTs
202	15617	AA875620	General		ESTs
202	15618	AA875620	General		ESTs
203	5384	AA891041	f, cc, General	jun B proto-oncogene	jun B proto-oncogene
204	24814	AA891209	f, p		ESTs, Moderately similar to R33729
					1, partial CDS [ H. sapiens ]
205	21930	AA891322	d		ESTs, Weakly similar to AF151373 1
					nucleolin-related protein NRP
					[ R. norvegicus ]
206	17225	AA891553	h		ESTs, Highly similar to elF3 p66
					[ M. musculus ]
207	7522	AA891571	j, m		ESTs, Weakly similar to S67314
					regulatory protein RMS1 - yeast
					( Saccharomyces cerevisiae )
					[ S. cerevisiae ]
208	9071	AA891578	b		ESTs
209	19321	AA891666	u	melanoma antigen, family D, 1	melanoma antigen, family D, 1
210	17693	AA891737	j, l, m, n, y, z		ESTs
211	17256	AA891739	General		ESTs, Weakly similar to T22521
					hypothetical protein F52H3.5 -
					Caenorhabditis elegans [ C. elegans ]
213	18269	AA891769	General		ESTs, Moderately similar to FINC RAT
					FIBRONECTIN PRECURSOR
					[ R. norvegicus ]
214	9905	AA891774	s, bb,		ESTs
			D239General
215	17061	AA891812	d		ESTs, Highly similar to alpha-adducin,
					hypertensive phenotype
					[ R. norvegicus ]
216	7050	AA891824	h		Rattus norvegicus clone ZG52 mRNA
					sequence
217	4463	AA891831	General		ESTs, Weakly similar to PE2R RAT 20
					ALPHA-HYDROXYSTEROID
					DEHYDROGENASE [ R. norvegicus ]
218	14289	AA891838	i		ESTs, Highly similar to muscle protein
					684 [ M. musculus ]
219	20523	AA891842	r, cc		ESTs
220	17779	AA891914	g, s, z		ESTs, Moderately similar to
					ACY1_HUMAN AMINOACYLASE-1
					[ H. sapiens ]
221	17438	AA891943	General		ESTs
222	22862	AA891944	p		ESTs
223	1159	AA891949	e, z		ESTs
224	4473	AA891965	General		ESTs, Weakly similar to T31496
					hypothetical protein Y116A8C.25 -
					Caenorhabditis elegans [ C. elegans ]
225	6362	AA892053	f, j, l, m		ESTs, Highly similar to chromatin
					structural protein homolog Supt5hp
					[ M. musculus ]
226	9037	AA892066	y		ESTs
227	19469	AA892112	General		ESTs, Weakly similar to proline
					dehydrogenase [ M. musculus ]
228	14595	AA892128	o, t, v		ESTs
229	16527	AA892154	cc		ESTs
230	4482	AA892173	bb		EST
231	20917	AA892238	h		ESTs
232	2357	AA892268	d		ESTs, Weakly similar to PC4221
					protein-tyrosine kinase [ R. norvegicus ]
233	18183	AA892271	h		ESTs
234	6523	AA892299	d		ESTs
236	13647	AA892367	a		ESTs, Highly similar to RL3 RAT 60S
					RIBOSOMAL PROTEIN L3
					[ R. norvegicus ]
237	3473	AA892378	v		ESTs, Highly similar to AF151893 1
					CGI-135 protein [ H. sapiens ]
238	17682	AA892382	j, p, s, x,		ESTs, Moderately similar to AF185570
			General		1 putative N-acetyltransferase
					Camello 4 [ R. norvegicus ]
239	820	AA892395	g, s	Aldolase B, fructose-	Aldolase B, fructose-biphosphate
				biphosphate
240	14754	AA892414	u		ESTs
241	17439	AA892446	f		ESTs
242	16469	AA892462	p		ESTs, Moderately similar to
					UCRY_HUMAN UBIQUINOL-
					CYTOCHROME C REDUCTASE
					COMPLEX 6.4 KD PROTEIN
					[ H. sapiens ]
243	13609	AA892468	i, General		Rattus norvegicus mRNA for prostasin
					precursor, complete cds
243	13610	AA892468	n, v, General		Rattus norvegicus mRNA for prostasin
					precursor, complete cds
244	9254	AA892470	n, u		ESTs, Highly similar to HISTONE
					H2A.Z [ R. norvegicus ]
245	11991	AA892483	s		ESTs
246	1522	AA892486	f		ESTs, Moderately similar to LYAG
					MOUSE LYSOSOMAL ALPHA-
					GLUCOSIDASE PRECURSOR
					[ M. musculus ]
247	11994	AA892507	aa		ESTs, Moderately similar to S63540
					protein DS 1, 24K [ H. sapiens ]
248	23888	AA892520	w		ESTs
248	23889	AA892520	h		ESTs
249	8599	AA892522	p		ESTs
250	15154	AA892532	p		R. norvegicus (Wistar) CaBP1 mRNA
251	17468	AA892545	r		ESTs, Highly similar to multi-
					membrane spanning polyspecific
					transporter [ M. musculus ]
252	11203	AA892554	f, h		ESTs, Highly similar to ras-GTPase-
					activating protein SH3-domain binding
					protein [ M. musculus ]
253	18906	AA892561	a, bb,		ESTs, Moderately similar to PTD012
			General		[ H. sapiens ]
254	19327	AA892562	f, j, y, z		R. norvegicus mRNA for nucleolar
					protein NAP57
255	18274	AA892572	p		ESTs
256	4512	AA892578	cc		ESTs
257	15876	AA892582	w		ESTs, Highly similar to RL8_HUMAN
					60S RIBOSOMAL PROTEIN L
					[ R. norvegicus ]
258	19085	AA892598	General		ESTs
258	19086	AA892598	General		ESTs
259	20065	AA892647	l		ESTs, Highly similar to H4_HUMAN
					HISTONE H4 [ R. norvegicus ]
260	20088	AA892666	a, n		ESTs
261	23783	AA892773	n		ESTs
262	17549	AA892776	f, z		Rat mitochondrial proton/phosphate
					symporter mRNA, complete cds
263	13542	AA892798	b		ESTs
264	22537	AA892799	General	HHs: glyoxylate	ESTs, Weakly similar to SERA RAT D-
				reductase/hydroxypyruvate	3-PHOSPHOGLYCERATE
				reductase	DEHYDROGENASE [ R. norvegicus ]
264	22539	AA892799	v	HHs: glyoxylate	ESTs, Weakly similar to SERA RAT D-
				reductase/hydroxypyruvate	3-PHOSPHOGLYCERATE
				reductase	DEHYDROGENASE [ R. norvegicus ]
264	22538	AA892799	General	HHs: glyoxylate	ESTs, Weakly similar to SERA RAT D-
				reductase/hydroxypyruvate	3-PHOSPHOGLYCERATE
				reductase	DEHYDROGENASE [ R. norvegicus ]
265	6951	AA892820	h		ESTs, Weakly similar to S70642
					ubiquitin ligase Nedd4 - rat
					[ R. norvegicus ]
266	23322	AA892821	j, z		Rattus norvegicus aiar mRNA for
					androgen-inducible aldehyde
					reductase, complete cds
267	17923	AA892843	f		ESTs, Weakly similar to T29904
					hypothetical protein F59A3.3 -
					Caenorhabditis elegans [ C. elegans ]
268	22871	AA892859	m		ESTs, Weakly similar to procollagen-
					lysine 5-dioxygenase [ R. norvegicus ]
269	9053	AA892861	p, v,		ESTs
			General
270	16482	AA892940	w		ESTs, Weakly similar to EF2 RAT
					ELONGATION FACTOR 2
					[ R. norvegicus ]
271	12020	AA893035	j, y		Rattus norvegicus HP33 mRNA,
					complete cds
272	3863	AA893060	General		ESTs
273	13332	AA893080	i, General		ESTs
274	21305	AA893082	General		ESTs
275	16591	AA893191	j, z		ESTs
276	17447	AA893192	General		ESTs
277	3876	AA893205	n		ESTs
278	3878	AA893230	General		ESTs, Weakly similar to
					CALM_HUMAN CALMODULIN
					[ R. norvegicus ]
279	20986	AA893242	q	Acyl CoA synthetase, long	Acyl CoA synthetase, long chain
				chain
280	16168	AA893280	i, z,		ESTs, Moderately similar to
			General		adipophilin [ H. sapiens ]
281	3886	AA893289	j, m, y		ESTs
282	15209	AA893327	y		ESTs
283	17800	AA893436	cc		ESTs
284	17836	AA893626	h		ESTs, Weakly similar to LIS1 MOUSE
					PLATELET-ACTIVATING FACTOR
					ACETYLHYDROLASE IB ALPHA
					SUBUNIT [ R. norvegicus ]
285	9084	AA893717	x		ESTs
286	22731	AA893743	d		ESTs
287	12031	AA893860	v	HHs: threonyl-tRNA	ESTs, Moderately similar to
				synthetase	SYTC_HUMAN THREONYL-TRNA
					SYNTHETASE, CYTOPLASMIC
					[ H. sapiens ]
288	17897	AA893905	k		ESTs
289	3447	AA893982	d		ESTs
290	22583	AA894009	n
291	10540	AA894027	j		EST
292	4569	AA894059	x		ESTs, Highly similar to A55748
					protein kinase [ M. musculus ]
293	18419	AA894130	d		ESTs, Weakly similar to APP2 RAT
					AMYLOID-LIKE PROTEIN 2
					PRECURSOR [ R. norvegicus ]
294	17336	AA894297	j		ESTs
295	19120	AA894318	f, j		ESTs
296	19762	AA899113	i		ESTs
297	18286	AA899219	u		Rat mRNA for beta-tubulin T beta15
298	22051	AA899498	w		ESTs, Weakly similar to T26581
					hypothetical protein Y32B12A.3 -
					Caenorhabditis elegans [ C. elegans ]
298	22052	AA899498	q		ESTs, Weakly similar to T26581
					hypothetical protein Y32B12A.3 -
					Caenorhabditis elegans [ C. elegans ]
299	21628	AA899563	aa		ESTs
300	4262	AA899590	i		ESTs
301	4661	AA899709	t, General	receptor activity modifying	receptor activity modifying protein 3
				protein 3
302	21354	AA899721	q		ESTs
303	17905	AA899762	General		Rattus norvegicus epidermal growth
					factor receptor related protein (Errp)
					mRNA, complete cds
304	15231	AA899840	r		ESTs
305	23778	AA899854	c, k, x	topoisomerase (DNA) II	topoisomerase (DNA) II alpha
				alpha
306	22060	AA899898	b		ESTs
307	9114	AA899951	v, General		ESTs
308	8988	AA900148	f		ESTs
309	11841	AA900247	v		Rattus norvegicus mRNA for
					Hsp70/Hsp90 organizing protein
310	4725	AA900290	cc		ESTs, Highly similar to ALPHA-2-
					MACROGLOBULIN PRECURSOR
					[ R. norvegicus ]
311	4747	AA900465	General		ESTs
312	20988	AA900562	o		ESTs
313	3822	AA900863	b, g,		ESTs, Weakly similar to nuclear RNA
			General		helicase [ R. norvegicus ]
315	12420	AA901017	b		ESTs, Weakly similar to T20702
					hypothetical protein F10C2.6 -
					Caenorhabditis elegans [ C. elegans ]
316	4849	AA901155	s		Rattus norvegicus CDK105 mRNA
317	3959	AA901338	General		ESTs, Highly similar to IF2B_HUMAN
					EUKARYOTIC TRANSLATION
					INITIATION FACTOR 2 BETA
					SUBUNIT [ H. sapiens ]
318	22846	AA923982	a, d		ESTs, Highly similar to ATP-specific
					succinyl-CoA synthetase beta subunit
					[ M. musculus ]
319	4895	AA923999	k		ESTs
320	21546	AA924188	cc,		ESTs
			General
321	24192	AA924210	n, General		ESTs
322	4933	AA924301	g, l, General		EST
323	4944	AA924405	l, General		ESTs, Moderately similar to
					NO56_HUMAN NUCLEOLAR
					PROTEIN NOP56 [ H. sapiens ]
324	4948	AA924428	r		ESTs
325	4949	AA924432	General		ESTs, Weakly similar to NPT2 RAT
					RENAL SODIUM-DEPENDENT
					PHOSPHATE TRANSPORT
					PROTEIN 2 [ R. norvegicus ]
326	18891	AA924598	e		ESTs
327	22540	AA924630	v, General	HHs: glyoxylate	ESTs, Weakly similar to SERA RAT D-
				reductase/hydroxypyruvate	3-PHOSPHOGLYCERATE
				reductase	DEHYDROGENASE [ R. norvegicus ]
327	22541	AA924630	General	HHs: glyoxylate	ESTs, Weakly similar to SERA RAT D-
				reductase/hydroxypyruvate	3-PHOSPHOGLYCERATE
				reductase	DEHYDROGENASE [ R. norvegicus ]
328	14759	AA924766	k		ESTs
329	23123	AA924794	x		ESTs
330	4067	AA924813	g, p		ESTs
331	2888	AA924902	r, General		ESTs
332	18130	AA924964	d		ESTs, Highly similar to sec7 domain
					family member [ H. sapiens ]
333	23141	AA925019	r		ESTs
334	23195	AA925026	General		ESTs, Weakly similar to MCT7 RAT
					MAST CELL PROTEASE 7
					PRECURSOR [ R. norvegicus ]
335	21458	AA925049	f, aa,		ESTs
			General
336	5073	AA925061	m		ESTs, Moderately similar to S20710
					hypothetical protein, 16K - mouse
					[ M. musculus ]
337	14790	AA925087	o, General		ESTs
338	5089	AA925126	g		EST, Highly similar to T50621
					hypothetical protein DKFZp762O076.1
					[ H. sapiens ]
339	23261	AA925145	k, General		ESTs, Moderately similar to BHMT
					RAT BETAINE-HOMOCYSTEINE S-
					METHYLTRANSFERASE
					[ R. norvegicus ]
340	17363	AA925150	a		ESTs, Moderately similar to
					neurodegeneration-associated protein
					1 [ R. norvegicus ]
341	23448	AA925167	l		ESTs
342	23159	AA925318	e	l-kappa-B-beta	l-kappa-B-beta
343	21500	AA925353	k		ESTs
344	22479	AA925418	t		ESTs
345	21151	AA925539	b		ESTs
346	16944	AA925541	f	heterogeneous nuclear	heterogeneous nuclear
				ribonucleoprotein L	ribonucleoprotein L
346	16945	AA925541	t	heterogeneous nuclear	heterogeneous nuclear
				ribonucleoprotein L	ribonucleoprotein L
347	17514	AA925554	bb	HHs: succinate	ESTs, Highly similar to
				dehydrogenase complex,	DHSA_HUMAN SUCCINATE
				subunit A, flavoprotein (Fp)	DEHYDROGENASE [ H. sapiens ]
348	5183	AA925662	i, General		ESTs
349	23189	AA925844	r		ESTs
350	23190	AA925863	aa		ESTs, Highly similar to IMB3_HUMAN
					IMPORTIN BETA-3 SUBUNIT
					[ H. sapiens ]
351	5252	AA926051	General		EST
352	22967	AA926080	h, cc		ESTs
353	17157	AA926129	b		ESTs
354	13411	AA926196	u, General		ESTs
355	5295	AA926247	General	putative potassium channel	putative potassium channel TWIK
				TWIK
356	22928	AA926262	General		ESTs, Moderately similar to
					NEURONAL PROTEIN 3.1
					[ M. musculus ]
357	8948	AA926316	r		ESTs, Moderately similar to T13963
					formin related protein, lymphocyte
					specific - mouse [ M. musculus ]
358	21798	AA926365	aa		ESTs, Moderately similar to AF151827
					1 CGI-69 protein [ H. sapiens ]
359	9942	AA942697	s		ESTs
360	6039	AA942716	x, General		ESTs, Highly similar to HN1
					[ M. musculus ]
361	11174	AA942745	g, o, w		ESTs
362	23005	AA942770	g		ESTs
363	21318	AA942774	General		ESTs
364	6615	AA942889	v		ESTs, Weakly similar to T26686
					hypothetical protein Y38F1A.6 -
					Caenorhabditis elegans [ C. elegans ]
365	6691	AA943028	c		ESTs, Highly similar to KFMS RAT
					MACROPHAGE COLONY
					STIMULATING FACTOR I
					RECEPTOR PRECURSOR
					[ R. norvegicus ]
366	22142	AA943066	p		ESTs, Weakly similar to p68 RNA
					helicase [ R. norvegicus ]
367	21993	AA943149	v, General		ESTs, Weakly similar to T00084
					hypothetical protein KIAA0512
					[ H. sapiens ]
368	9061	AA943508	General		ESTs, Weakly similar to T08666
					hypothetical protein
					DKFZp547N0510.1 [ H. sapiens ]
369	24390	AA943531	b, j, n, y		ESTs, Weakly similar to VIL1 MOUSE
					VILLIN [ M. musculus ]
370	13976	AA943532	f, s, x		Rattus norvegicus mRNA for class I
					beta-tubulin, complete cds
371	22248	AA943537	cc,		Rattus norvegicus zyxin mRNA, partial
			General		cds
372	22257	AA943558	m		ESTs, Highly similar to T2DA_HUMAN
					TRANSCRIPTION INITIATION
					FACTOR TFIID 20/15 KDA
					SUBUNITS [ H. sapiens ]
373	12673	AA943773	u, cc,		ESTs
			General
374	13641	AA944154	u		ESTs
375	2658	AA944155	f		ESTs
376	12770	AA944161	d		ESTs
377	20903	AA944180	i, x		ESTs, Highly similar to CKS2 MOUSE
					CYCLIN-DEPENDENT KINASES
					REGULATORY SUBUNIT 2
					[ M. musculus ]
378	13507	AA944244	v		ESTs
379	15596	AA944353	General		ESTs
380	22681	AA944413	i, v, cc,		ESTs
			General
381	6711	AA944439	General		ESTs, Highly similar to hypothetical
					protein [ M. musculus ]
382	14763	AA944481	i, q,		ESTs, Weakly similar to FIBA RAT
			General		FIBRINOGEN ALPHA/ALPHA-E
					CHAIN PRECURSOR [ R. norvegicus ]
383	22466	AA944605	h		ESTs
384	12301	AA944727	b		ESTs, Weakly similar to A44437
					regenerating liver inhibitory factor
					RL/IF-1 - rat [ R. norvegicus ]
385	7023	AA944792	d, m, aa	HHs: polymerase (RNA) II	ESTs, Highly similar to RNA
				(DNA directed) polypeptide E	polymerase II 23 kD subunit
				(25 kD)	[ H. sapiens ]
386	22536	AA944803	bb		ESTs
387	22501	AA944811	g, l		ESTs
388	23967	AA944831	s		ESTs
389	26084	AA944922	i
390	11974	AA944958	General		ESTs
391	22547	AA944970	aa		ESTs
392	22554	AA945076	z, General		ESTs
393	14352	AA945181	General		ESTs
395	1798	AA945569	General		R. norvegicus alpha-1-macroglobulin
					mRNA, complete cds
396	22050	AA945604	i, aa		ESTs
397	19731	AA945615	d, o		ESTs
398	22612	AA945624	a, General		ESTs, Weakly similar to DHQU RAT
					NAD(P)H DEHYDROGENASE
					[ R. norvegicus ]
399	22618	AA945656	aa		ESTs
400	11871	AA945679	v		ESTs
401	22656	AA945818	General		ESTs
402	6720	AA945828	p		ESTs
403	22351	AA945867	m		ESTs
404	22665	AA945877	f		ESTs
405	24243	AA945950	b		ESTs
406	22689	AA945962	General		ESTs
407	22692	AA945986	d		ESTs
408	22696	AA945996	c, General		ESTs
408	22697	AA945996	c, o		ESTs
409	22658	AA945998	w		ESTs
410	20832	AA946040	s	HMm: RIKEN cDNA	ESTs, Highly similar to COXG
				2010000G05 gene	MOUSE CYTOCHROME C OXIDASE
					POLYPEPTIDE VIB [ M. musculus ]
411	18337	AA946046	General		ESTs
412	825	AA946108	General		Rattus norvegicus laminin-5 alpha 3
					chain mRNA, complete cds
413	8639	AA946221	e, cc,		ESTs
			General
414	23237	AA946224	f		ESTs
415	15600	AA946250	o, aa		ESTs
416	19387	AA946275	t		ESTs, Highly similar to AR21_HUMAN
					ARP2/3 COMPLEX 21 KD SUBUNIT
					[ H. sapiens ]
417	6351	AA946344	d	PCTAIRE-1 protein kinase,	PCTAIRE-1 protein kinase,
				alternatively spliced	alternatively spliced
418	22057	AA946348	e		ESTs, Highly similar to autoantigen
					[ H. sapiens ]
419	22069	AA946349	aa		ESTs
420	13962	AA946351	General		ESTs
421	18280	AA946361	g		ESTs, Highly similar to Ring3
					[ M. musculus ]
422	18944	AA946391	v		ESTs
424	21410	AA946408	t		ESTs, Moderately similar to p18
					component of aminoacyl-tRNA
					synthetase complex [ H. sapiens ]
425	643	AA946439	o, y		Rat H4 gene for somatic histone H4
426	20736	AA946443	x		ESTs, Highly similar to NPD1 MOUSE
					NEURAL PROLIFERATION
					DIFFERENTIATION AND CONTROL
					PROTEIN-1 PRECURSOR
					[ M. musculus ]
427	21878	AA946448	r		ESTs
428	21947	AA946451	bb		ESTs, Highly similar to AF151863 1
					CGI-105 protein [ H. sapiens ]
429	17499	AA946467	General		ESTs
430	1809	AA946503	x, General		Rat mRNA for alpha-2u globulin-
					related protein
431	23360	AA955104	f		ESTs
432	23471	AA955162	General		ESTs
433	9452	AA955206	b, General		ESTs
434	23512	AA955282	General		ESTs
435	22596	AA955298	General		ESTs
436	23283	AA955391	h	lipoprotein-binding protein	lipoprotein-binding protein
437	23546	AA955393	General		ESTs
438	12404	AA955408	b		ESTs, Weakly similar to SX10 RAT
					TRANSCRIPTION FACTOR SOX-10
					[ R. norvegicus ]
439	23626	AA955540	aa		ESTs
441	17540	AA955914	bb		EST, EST, Moderately similar to FBRL
					MOUSE FIBRILLARIN
					[ M. musculus ], ESTs, Highly similar to
					FBRL MOUSE FIBRILLARIN
					[ M. musculus ]
442	24277	AA955962	General		ESTs
443	19939	AA955980	General		ESTs, Moderately similar to pescadillo
					[ H. sapiens ]
444	24000	AA956005	i		ESTs, Weakly similar to AF139894 1
					RNA-binding protein alpha-CP1
					[ M. musculus ]
445	11050	AA956164	s, v		ESTs, Weakly similar to TCPA RAT T-
					COMPLEX PROTEIN 1, ALPHA
					SUBUNIT [ R. norvegicus ]
446	498	AA956278	a, General		ESTs
447	23409	AA956294	q		ESTs
449	23773	AA956476	f, x		ESTs
450	23799	AA956530	d		ESTs, Highly similar to ET putative
					translation product [ M. musculus ]
451	23800	AA956534	aa		ESTs, Weakly similar to
					RNG1_HUMAN RING1 PROTEIN
					[ H. sapiens ]
452	23834	AA956659	cc,		EST
			General
453	16425	AA956688	f, x		ESTs, Moderately similar to C8
					[ M. musculus ]
454	23847	AA956723	s		EST
455	23852	AA956746	j, l, m, z		ESTs, Highly similar to Mi-2 protein
					[ H. sapiens ]
456	5989	AA956907	g, s		ESTs, Highly similar to p162 protein
					[ M. musculus ]
456	5990	AA956907	General		ESTs, Highly similar to p162 protein
					[ M. musculus ]
457	23957	AA957123	u, General		ESTs, Weakly similar to AF187065 1
					p75NTR-associated cell death
					executor [ R. norvegicus ]
458	22357	AA957264	General		ESTs, Highly similar to hypothetical
					protein [ H. sapiens ]
459	23314	AA957270	g, l, m, p, v,		ESTs
			cc,
			General
460	23995	AA957292	a, b		ESTs
461	2702	AA957307	General	HHs: seryl-tRNA synthetase	ESTs, Moderately similar to
					SYS_HUMAN SERYL-TRNA
					SYNTHETASE [ H. sapiens ]
462	24040	AA957422	c		ESTs, Highly similar to HIGH
					AFFINITY IMMUNOGLOBULIN
					EPSILON RECEPTOR GAMMA-
					SUBUNIT PRECURSOR
					[ R. norvegicus ]
463	12478	AA957554	m		ESTs, Highly similar to P3 MOUSE P3
					PROTEIN [ M. musculus ]
464	21306	AA957811	v		ESTs
465	24183	AA957889	t		ESTs
466	24178	AA957905	d		ESTs
467	17034	AA963071	e		ESTs, Highly similar to epsilon-COP
					[ M. musculus ]
468	24053	AA963092	General		ESTs, Weakly similar to AF187065 1
					p75NTR-associated cell death
					executor [ R. norvegicus ]
469	2767	AA963201	o		ESTs
470	2022	AA963259	g		ESTs
471	2126	AA963488	d		ESTs
472	24246	AA963703	b		ESTs, Highly similar to cell cycle
					protein p38-2G4 homolog [ H. sapiens ]
473	2195	AA963746	General		ESTs
474	19370	AA963797	i		ESTs
475	2282	AA964147	e		ESTs
476	2284	AA964152	x		EST
478	2350	AA964368	g, General		ESTs, Highly similar to TGT_HUMAN
					QUEUINE TRNA-
					RIBOSYLTRANSFERASE [ H. sapiens ]
479	18830	AA964496	aa		ESTs, Highly similar to ATRTC actin
					beta - rat [ R. norvegicus ]
480	2392	AA964541	b		EST
481	2395	AA964554	General		ESTs, Highly similar to U3 snoRNP
					associated 55 kDa protein [ H. sapiens ]
482	2410	AA964589	i, aa		EST
483	19145	AA964613	t		ESTs
484	2424	AA964617	g		ESTs
485	3107	AA964687	General		ESTs
486	2457	AA964752	q, t		EST
487	6778	AA964763	b		ESTs, Highly similar to DRIM protein
					[ H. sapiens ]
489	2468	AA964807	l		ESTs, Weakly similar to T23337
					hypothetical protein K05C4.2 -
					Caenorhabditis elegans [ C. elegans ]
490	2469	AA964814	w	Glutamate-cysteine ligase	Glutamate-cysteine ligase (gamma-
				(gamma-glutamylcysteine	glutamylcysteine synthetase),
				synthetase), regulatory	regulatory
491	12561	AA964815	General		ESTs
492	2326	AA964892	aa		ESTs, Highly similar to
					PROCOLLAGEN ALPHA 1(IV) CHAIN
					PRECURSOR [ M. musculus ]
493	21339	AA964962	General		ESTs, Highly similar to ABC1 MOUSE
					ATP-BINDING CASSETTE, SUB-
					FAMILY A, MEMBER 1 [ M. musculus ]
494	21390	AA964988	General		ESTs
495	12569	AA965023	g		ESTs
496	2583	AA965166	bb		ESTs, Moderately similar to inorganic
					pyrophosphatase [ H. sapiens ]
497	15885	AA965207	r		ESTs, Highly similar to KIAA0958
					protein [ H. sapiens ]
499	2905	AA996727	b, l, m, u,		ESTs
			General
500	2915	AA996782	u, bb		ESTs, Moderately similar to S27267
					lamin A - rat [ R. norvegicus ]
501	2920	AA996813	d		ESTs
502	19525	AA996856	aa, General		EST
503	2984	AA997015	c		ESTs
504	2986	AA997028	General		ESTs
505	3145	AA997237	General		ESTs
506	19249	AA997342	m		ESTs
507	16883	AA997345	General		ESTs, Weakly similar to nitrilase
					homolog 1 [ M. musculus ]
508	12598	AA997362	s		ESTs, Moderately similar to
					LONN_HUMAN MITOCHONDRIAL
					LON PROTEASE HOMOLOG
					PRECURSOR [ H. sapiens ]
509	3470	AA997374	p		ESTs, Weakly similar to LIS1 MOUSE
					PLATELET-ACTIVATING FACTOR
					ACETYLHYDROLASE IB ALPHA
					SUBUNIT [ R. norvegicus ]
510	3180	AA997425	t		ESTs
511	3245	AA997608	General		ESTs, Weakly similar to PAI2 RAT
					PLASMINOGEN ACTIVATOR
					INHIBITOR-2, TYPE A [ R. norvegicus ]
512	3020	AA997656	t		ESTs, Moderately similar to T09071
					SH3 domains-containing protein
					POSH - mouse [ M. musculus ]
513	3269	AA997800	x, aa		ESTs, Moderately similar to T30249
					cell proliferation antigen Ki-67 - mouse
					[ M. musculus ]
514	3288	AA997877	f		ESTs
515	23992	AA998164	k, x	Cyclin B1	Cyclin B1
516	17470	AA998264	b		ESTs, Moderately similar to
					FLRE_HUMAN FLAVIN REDUCTASE
					[ H. sapiens ]
517	3773	AA998356	General		ESTs, Weakly similar to
					BCL3_HUMAN B-CELL LYMPHOMA
					3-ENCODED PROTEIN [ H. sapiens ]
518	19623	AA998422	General		EST
519	3572	AA998516	x		ESTs, Highly similar to CGA2 MOUSE
					CYCLIN A2 [ M. musculus ]
520	2782	AA998565	c		ESTs, Moderately similar to CYCLIN-
					DEPENDENT KINASE INHIBITOR 1C
					[ M. musculus ]
521	26119	AA998576	i, r, w,
			General
522	22737	AA998660	aa		ESTs
523	3696	AA999030	e		ESTs, Moderately similar to AF132966
					1 CGI-32 protein [ H. sapiens ]
524	3079	AA999169	k, x,		ESTs
			General
525	3081	AA999171	e, p, r	Signal transducer and	Signal transducer and activator of
				activator of transcription 1	transcription 1
526	3082	AA999172	General	HHs: guanine monophosphate	ESTs, Highly similar to
				synthetase	GUAA_HUMAN GMP SYNTHASE
					[ H. sapiens ]
527	17337	AB000717	k		ESTs
528	1535	AB000778	a	Phoshpolipase D gene 1	Phoshpolipase D gene 1
529	1382	AB002406	k	RuvB-like protein 1	RuvB-like protein 1
530	20184	AB003753	d
531	4312	AB010635	c, i, j, k, y, z		Rattus norvegicus mRNA for
					carboxylesterase precursor, complete
					cds
532	21666	AB012214	k	HMm: DNA methyltransferase	ESTs, Highly similar to JE0378 DNA
				(cytosine-5) 1	[ R. norvegicus ]
533	15772	AB015645	g		Rattus norvegicus mRNA for G protein
					coupled receptor, complete cds
534	1183	AF013144	h		Rattus norvegicus MAP-kinase
					phosphatase (cpg21) mRNA,
					complete cds
535	1582	AF015911	h, z		Rattus norvegicus NAC-1 protein
					(NAC-1) mRNA, complete cds
536	11483	AF020618	u, cc,		ESTs, Moderately similar to MY16
			General		MOUSE MYELOID
					DIFFERENTIATION PRIMARY
					RESPONSE PROTEIN MYD116
					[ M. musculus ], Rattus norvegicus
					progression elevated gene 3 protein
					mRNA, complete cds
537	20295	AF024712	aa		Rattus norvegicus MHC class lb M4
					(RT1.M4) pseudogene, complete
					sequence
538	19077	AF030358	y, z		Rattus norvegicus chemokine CX3C
					mRNA, complete cds
539	23044	AF034218	General	hyaluronidase 2	hyaluronidase 2
540	25178	AF035955	d
541	1564	AF035963	x, bb,		Rattus norvegicus kidney injury
			General		molecule-1 (KIM-1) mRNA, complete
					cds
542	8426	AF036335	f		Rattus norvegicus NonO/p54nrb
					homolog mRNA, partial cds
543	21817	AF036537	k		Rattus norvegicus homocysteine
					respondent protein HCYP2 mRNA,
					complete cds
544	21145	AF038571	General	Solute carrier family 1 A1	Solute carrier family 1 A1 (brain
				(brain glutamate transporter)	glutamate transporter)
545	22602	AF044574	General	putative peroxisomal 2,4-	putative peroxisomal 2,4-dienoyl-CoA
				dienoyl-CoA reductase	reductase
546	13464	AF047707	h	UDP-glucose: ceramide	UDP-glucose: ceramide
				glycosyltransferase	glycosyltransferase
547	24024	AF052695	x	cell cycle protein p55CDC	cell cycle protein p55CDC
548	12259	AF061266	h	transient receptor protein 1	Rattus norvegicus trp1 beta variant
					mRNA, complete cds
549	4589	AF062389	y, z		Rattus norvegicus kidney-specific
					protein (KS) mRNA, complete cds
550	16007	AF062594	t	nucleosome assembly	Rattus norvegicus nucleosome
				protein 1-like 1	assembly protein mRNA, complete
					cds
551	15761	AF062741	u		Rattus norvegicus pyruvate
					dehydrogenase phosphatase
					isoenzyme 2 mRNA, complete cds
552	17426	AF073839	p		Rattus norvegicus bithoraxoid-like
					protein mRNA, complete cds
553	18615	AF074608	s	RT1 class lb gene	RT1 class lb gene
554	15797	AF084205	f		Rattus norvegicus serine/threonine
					protein kinase TAO1 mRNA, complete
					cds
555	12932	AF102552	s	ankyrin 3 (G)	Rattus norvegicus 190 kDa ankyrin
					isoform mRNA, complete cds
556	18603	AI007649	x		ESTs, Highly similar to A49013 tumor
					cell suppression protein HTS1
					[ H. sapiens ]
557	22733	AI007668	r		ESTs
558	22746	AI007672	r		ESTs
559	24109	AI007725	General		ESTs
560	15848	AI007820	n, v		ESTs, ESTs, Highly similar to HS9B
					RAT HEAT SHOCK PROTEIN HSP
					90-BETA [ R. norvegicus ]
561	10108	AI007857	f	Hrs	Hrs
562	6804	AI007877	General		ESTs
563	20099	AI007893	f, u		ESTs
564	11368	AI007948	d		ESTs, Weakly similar to T18778
					hypothetical protein B0513.2b -
					Caenorhabditis elegans [ C. elegans ]
565	15849	AI008074	h		ESTs, ESTs, Highly similar to HS9B
					RAT HEAT SHOCK PROTEIN HSP
					90-BETA [ R. norvegicus ]
566	3121	AI008160	General		ESTs, Moderately similar to AF1518411
					CGI-83 protein [ H. sapiens ]
567	16646	AI008190	t		ESTs, Highly similar to Chain G, G
					Protein Heterotrimer Gi alpha 1 Beta 1
					Gamma 2 With Gdp Bound
					[ R. norvegicus ]
568	12683	AI008203	x		ESTs, Weakly similar to G2/MITOTIC-
					SPECIFIC CYCLIN B1 [ R. norvegicus ]
569	22018	AI008309	b		ESTs, Moderately similar to PIM1 RAT
					PROTO-ONCOGENE
					SERINE/THREONINE-PROTEIN
					KINASE PIM-1 [ R. norvegicus ]
570	23917	AI008441	n		ESTs, Highly similar to
					6PGD_HUMAN 6-
					PHOSPHOGLUCONATE
					DEHYOROGENASE,
					DECARBOXYLATIN [ H. sapiens ]
571	22599	AI008458	General		ESTs
572	22698	AI008578	p, General		ESTs
573	14405	AI008579	r, x		ESTs
574	4086	AI008629	x		ESTs, Moderately similar to JH0446
					75K autoantigen [ H. sapiens ]
575	3808	AI008643	i, v,		ESTs, Weakly similar to heat shock
			General		protein hsp40-3 [ M. musculus ]
576	3931	AI008697	l		ESTs, Weakly similar to T29897
					hypothetical protein F38A5.1 -
					Caenorhabditis elegans [ C. elegans ]
577	7785	AI008758	aa	Dipeptidyl peptidase 4	Dipeptidyl peptidase 4
578	16701	AI008838	q		ESTs, Weakly similar to
					LONN_HUMAN MITOCHONDRIAL
					LON PROTEASE HOMOLOG
					PRECURSOR [ H. sapiens ]
579	21789	AI008930	k		ESTs, Weakly similar to CYSR RAT
					CYSTEINE-RICH PROTEIN 1
					[ R. norvegicus ]
580	21895	AI008971	General		ESTs
581	410	AI008974	i, aa,		R. norvegicus mRNA encoding 45 kDa
			General		protein which binds to heymann
					nephritis antigen gp330
582	21632	AI009167	General		ESTs, Highly similar to BAG-family
					molecular chaperone regulator-2
					[ H. sapiens ]
583	21596	AI009168	General		ESTs
584	22801	AI009197	General		ESTs
585	11876	AI009321	cc,		ESTs, Highly similar to similar to
			General		human DNA-binding protein 5
					[ H. sapiens ]
586	2506	AI009341	General		ESTs
587	6382	AI009362	General		ESTs
588	14370	AI009427	k		ESTs, Highly similar to Lmp10
					proteasome subunit [ M. musculus ]
589	19275	AI009460	x		ESTs, Highly similar to filamin
					[ H. sapiens ]
590	4154	AI009467	g		ESTs
591	3464	AI009589	cc		ESTs
592	3926	AI009592	e		ESTs, Highly similar to molybdopterin-
					synthase large subunit [ M. musculus ]
593	19358	AI009675	c		EST
594	22545	AI009747	g		ESTs
595	15089	AI009752	cc,		ESTs
			General
596	5458	AI009756	h	ALG-2 interacting protein 1	ALG-2 interacting protein 1
597	6844	AI009770	e, r, cc		ESTs
598	15627	AI009810	aa		ESTs, Highly similar to RS16_HUMAN
					40S RIBOSOMAL PROTEIN S1
					[ R. norvegicus ]
599	22619	AI009825	d		ESTs
600	7857	AI009898	j, l, m, z		ESTs
601	13259	AI009946	r		ESTs
602	21105	AI010067	General		ESTs
603	24627	AI010102	aa	Testis enhanced gene	Testis enhanced gene transcript
				transcript
604	12716	AI010178	General		ESTs, Moderately similar to
					YA00_HUMAN HYPOTHETICAL
					PROTEIN CGI-100 PRECURSOR
					[ H. sapiens ]
605	18757	AI010216	aa		ESTs
606	2912	AI010220	aa,		ESTs, Weakly similar to claudin-7
			General		[ R. norvegicus ]
607	3316	AI010237	t		ESTs
608	15644	AI010256	General		R. norvegicus mRNA for histone H3.3
609	657	AI010262	b		Rattus norvegicus mRNA for
					inetrleukin-4 receptor (membrane-
					bound form), complete cds
610	3271	AI010303	b		ESTs
611	11081	AI010407	bb		ESTs, Moderately similar to
					erythroblast macrophage protein EMP
					[ H. sapiens ]
612	16521	AI010470	c, s, t,	Ceruloplasmin (ferroxidase)	Ceruloplasmin (ferroxidase)
			General
613	6927	AI010542	General		ESTs
614	17524	AI010568	a, j, y,	Growth hormone receptor	Growth hormone receptor
			General
615	6946	AI010642	n		ESTs
616	23509	AI010962	aa		ESTs, Highly similar to SDP3
					[ M. musculus ]
617	6044	AI011285	t		ESTs
618	13855	AI011361	o		ESTs
619	21779	AI011380	cc		ESTs
621	12534	AI011460	cc		ESTs
622	12629	AI011492	e, f		ESTs, Moderately similar to HYA22
					[ H. sapiens ]
623	735	AI011560	f		ESTs, Weakly similar to B Chain B,
					Solution Structure Of The C-Terminal
					Negative Regulatory Domain Of P53
					In A Complex With Ca2+-Bound
					S100b(Bb) [ R. norvegicus ]
624	3941	AI011598	General		ESTs, Moderately similar to LMA5
					MOUSE LAMININ ALPHA-5 CHAIN
					[ M. musculus ]
625	17550	AI011607	j, General		ESTs, Weakly similar to JE0360
					gamma-Butyrobetaine hydroxylase
					[ H. sapiens ]
626	10636	AI011634	e		ESTs, Weakly similar to I(3)S12
					protein [ D. melanogaster ]
627	3995	AI011678	General		ESTs
628	16112	AI011706	h		ESTs, Weakly similar to SFR5 RAT
					SPLICING FACTOR,
					ARGININE/SERINE-RICH 5
					[ R. norvegicus ]
629	13354	AI011757	c		ESTs, Weakly similar to A35902 Fc
					gamma [ R. norvegicus ]
630	12745	AI011799	cc		ESTs
631	18684	AI011812	t		ESTs, Highly similar to AF151842 1
					CGI-84 protein [ H. sapiens ]
632	4205	AI011982	b		ESTs
633	6518	AI012114	General		ESTs, Moderately similar to R29425 1
					[ H. sapiens ]
634	17407	AI012145	General		ESTs
635	13093	AI012177	r		ESTs, Weakly similar to PPP5 RAT
					SERINE/THREONINE PROTEIN
					PHOSPHATASE 5 [ R. norvegicus ]
636	15395	AI012216	f		ESTs, Moderately similar to
					Y33K_HUMAN HYPOTHETICAL 33.4 KDA
					PROTEI [ H. sapiens ]
637	21796	AI012221	d, General		ESTs, Weakly similar to S70484 RS43
					protein - rat (fragment) [ R. norvegicus ]
638	3981	AI012235	i, General		ESTs
639	6606	AI012308	i, r		ESTs
640	3417	AI012337	w		ESTs, Highly similar to NHPX RAT
					NHP2/RS6 FAMILY PROTEIN
					YEL026W HOMOLOG [ R. norvegicus ]
641	24200	AI012356	b, t,		ESTs
			General
642	7471	AI012379	cc		ESTs
643	7247	AI012438	g		ESTs
644	7127	AI012464	p, General		ESTs
645	3304	AI012471	b		ESTs, Weakly similar to T26998
					hypothetical protein Y48B6A.6 -
					Caenorhabditis elegans [ C. elegans ]
646	2311	AI012485	aa		ESTs
647	20817	AI012589	g, n, q	glutathione S-transferase, pi 2	glutathione S-transferase, pi 2
648	3493	AI012590	v, General		ESTs
649	8975	AI012613	General		ESTs
650	11335	AI012619	j		ESTs, Highly similar to unknown
					[ H. sapiens ]
651	21409	AI012637	General		ESTs
652	8015	AI012638	aa		ESTs, Moderately similar to AF151834
					1 CGI-76 protein [ H. sapiens ]
653	8476	AI012647	w		ESTs, Highly similar to RS20_HUMAN
					40S RIBOSOMAL PROTEIN S2
					[ R. norvegicus ]
654	4232	AI012958	e, p,		ESTs
			General
655	23128	AI013011	General		ESTs
656	20086	AI013260	General	lamin	lamin
657	11969	AI013273	k		ESTs, Highly similar to GLIA
					DERIVED NEXIN PRECURSOR
					[ R. norvegicus ]
658	26147	AI013387	aa
659	8815	AI013437	p		ESTs
660	19722	AI013508	k		Rattus norvegicus Hsp70 binding
					protein HspBP mRNA, complete cds
661	6674	AI013568	General		ESTs
662	23145	AI013647	o, t		ESTs
663	15130	AI013676	w		ESTs
664	7274	AI013715	aa		ESTs, Moderately similar to BMP6
					RAT BONE MORPHOGENETIC
					PROTEIN 6 PRECURSOR
					[ R. norvegicus ]
665	7276	AI013730	e		ESTs, Highly similar to KIAA1102
					protein [ H. sapiens ]
666	7278	AI013738	y, z, aa		ESTs
667	22592	AI013740	s, x, bb,		ESTs, Highly similar to proteolipid
			General		protein 2 [ M. musculus ]
668	16584	AI013765	w	Arrestin, beta 2	Arrestin, beta 2
669	24143	AI013804	j, l		ESTs, Highly similar to T27225 ADP-
					ribosylation factor Y57G11C.13
					[similarity] - Caenorhabditis elegans
					[ C. elegans ]
670	15928	AI013829	a, General		ESTs
671	21950	AI013861	j	3-hydroxyisobutyrate	3-hydroxyisobutyrate dehydrogenase
				dehydrogenase
672	3260	AI013875	t		ESTs
673	2708	AI013882	d, q		ESTs, Moderately similar to MSSP
					[ M. musculus ]
674	8585	AI013886	i		ESTs
675	7299	AI013911	p, r, t,		ESTs, Weakly similar to CIRP
			General		[ R. norvegicus ]
676	15904	AI013971	General		Rat ankyrin binding glycoprotein-1
					related mRNA sequence
677	12781	AI014023	w		ESTs, Moderately similar to R32184 1
					[ H. sapiens ]
678	19372	AI014135	aa		Rattus norvegicus mRNA for beta-
					carotene 15,15′-dioxygenase,
					complete cds
679	4241	AI014140	w		ESTs, Highly similar to hypothetical
					protein [ H. sapiens ]
680	15247	AI014169	c, u		Rattus norvegicus clone N27 mRNA
681	7315	AI028831	n		ESTs, Moderately similar to mitogen-
					activated protein kinase kinase kinase
					6 [ H. sapiens ]
682	16631	AI028856	General		ESTs
683	23297	AI028953	x		ESTs, Highly similar to S55054 Sm
					protein G [ H. sapiens ]
684	11326	AI029015	b		ESTs
685	2866	AI029058	n, y		ESTs
686	12812	AI029126	General		ESTs
687	17602	AI029156	p		ESTs
688	7392	AI029185	aa		EST
689	6517	AI029264	d, k, x		ESTs
690	7639	AI029292	b		ESTs
691	3874	AI029428	i, General		ESTs, Highly similar to CB80_HUMAN
					80 KDA NUCLEAR CAP BINDING
					PROTEIN [ H. sapiens ]
692	12819	AI029437	f		ESTs
693	7452	AI029466	r		ESTs
694	7493	AI029608	b		ESTs
696	7537	AI029829	o, General		ESTs
697	2310	AI029969	v		ESTs
698	7585	AI030023	x		ESTs
699	7586	AI030024	b, n		ESTs
700	14492	AI030091	cc		ESTs
701	10673	AI030134	f		ESTs, Weakly similar to ankyrin
					[ R. norvegicus ]
702	7615	AI030163	o, r		ESTs
703	2370	AI030179	General		ESTs
704	7681	AI030449	n		ESTs, Moderately similar to
					methyltransferase related protein
					[ M. musculus ]
705	11559	AI030472	General		ESTs
706	7665	AI030668	t, bb		Rattus norvegicus nucleosome
					assembly protein mRNA, complete
					cds
707	24222	AI030704	k		ESTs
708	10740	AI030743	h		EST
709	10742	AI030773	e		EST
711	16169	AI030932	General		ESTs, Moderately similar to
					adipophilin [ H. sapiens ]
712	19527	AI030991	f		EST
713	22614	AI031004	r		ESTs, Highly similar to SX17 MOUSE
					TRANSCRIPTION FACTOR SOX-17
					[ M. musculus ]
714	3167	AI031012	e		ESTs, Highly similar to CLPP MOUSE
					PUTATIVE ATP-DEPENDENT CLP
					PROTEASE PROTEOLYTIC
					SUBUNIT, MITOCHONDRIAL
					PRECURSOR [ M. musculus ]
715	5350	AI043611	a		ESTs
716	7858	AI043654	t		EST
717	10784	AI043678	d		EST
718	9180	AI043694	aa		ESTs, Weakly similar to T27134
					hypothetical protein Y53C12B.2 -
					Caenorhabditis elegans [ C. elegans ]
719	7867	AI043695	aa	HHs: phosphoribosyl	Rattus norvegicus mRNA for
				pyrophosphate	amidophosphoribosyltransferase
				amidotransferase
720	7584	AI043724	General		ESTs
721	7895	AI043768	e		ESTs, Highly similar to AF151810 1
					CGI-52 protein [ H. sapiens ]
722	7903	AI043805	General		ESTs
723	7913	AI043849	cc		ESTs, Weakly similar to ELL MOUSE
					RNA POLYMERASE II ELONGATION
					FACTOR ELL [ M. musculus ]
724	3899	AI043904	l		ESTs
725	6766	AI043914	f		ESTs
726	10818	AI043990	g, l, m,		ESTs
			General
727	7956	AI044018	f		EST
728	5393	AI044170	p		EST
729	5398	AI044177	q		EST
730	5425	AI044237	a, d		ESTs, Weakly similar to AF121893 1
					sequence-specific single-stranded-
					DNA-binding protein [ R. norvegicus ]
731	8692	AI044247	r		ESTs, Weakly similar to putative
					peroxisomal 2,4-dienoyl-CoA
					reductase [ R. norvegicus ]
732	5430	AI044253	i		EST
733	5461	AI044338	g, p,		ESTs
			General
734	5464	AI044345	i		ESTs
735	3359	AI044347	aa		ESTs
737	2695	AI044396	b		Rat (clones rLG[08, 14, 25]) interleukin
					6 signal transducer mRNA sequence
738	5494	AI044425	General		ESTs
740	9882	AI044588	j, m		ESTs
741	5575	AI044688	g		ESTs
742	2348	AI044794	General		ESTs
743	18205	AI044836	n		ESTs, Weakly similar to AF165892 1
					RNA-binding protein SiahBP
					[ R. norvegicus ]
744	5626	AI044864	u		ESTs
745	5630	AI044869	f		ESTs
746	5634	AI044683	General		ESTs, Moderately similar to AF151873
					1 CGI-115 protein [ H. sapiens ]
747	4047	AI044947	l, m		ESTs, Moderately similar to
					dJ1183I21.1 [ H. sapiens ]
748	5654	AI044976	w		EST
749	5684	AI045056	r		ESTs
750	19235	AI045074	General		ESTs, Highly similar to BGAL MOUSE
					BETA-GALACTOSIDASE
					PRECURSOR [ M. musculus ]
751	5689	AI045075	i, aa,		ESTs, Moderately similar to HEM45
			General		[ H. sapiens ]
752	5711	AI045151	General		ESTs, Moderately similar to AF118838
					1 citrin [ H. sapiens ]
753	19237	AI045153	c		ESTs, Weakly similar to TVRTK6
					ribosomal protein S6 kinase
					[ R. norvegicus ]
754	9964	AI045161	f		EST
755	5735	AI045223	f		ESTs
756	5474	AI045477	a, General		ESTs
757	5811	AI045502	d, e		ESTs
758	5819	AI045537	General		ESTs
759	5839	AI045594	i		ESTs
760	6808	AI045600	s		ESTs, Highly similar to S30034
					translocating chain-associating
					membrane protein [ H. sapiens ]
761	17755	AI045608	y		ESTs
763	10020	AI045632	a		ESTs
764	5855	AI045669	General		ESTs
765	5881	AI045789	i		ESTs, Weakly similar to T12540
					hypothetical protein DKFZp434J214.1
					[ H. sapiens ]
766	5897	AI045862	General		ESTs, Moderately similar to S64732
					scaffold attachment factor B
					[ H. sapiens ]
767	5900	AI045866	y, z		ESTs
768	7540	AI045882	o, t,		ESTs, Weakly similar to B48013
			General		proline-rich proteoglycan 2 precursor,
					parotid - rat [ R. norvegicus ]
769	5329	AI045970	p		ESTs
770	15093	AI058285	d		ESTs
771	8002	AI058304	i		ESTs
772	8017	AI058341	c		EST
773	6828	AI058359	General		ESTs, Weakly similar to T46465
					hypothetical protein
					DKFZp434A0530.1 [ H. sapiens ]
774	8177	AI058603	aa		ESTs
775	3090	AI058730	aa		ESTs
776	10093	AI058746	g		ESTs
777	8143	AI058759	General		ESTs
778	18659	AI058762	f		ESTs
779	8163	AI058837	aa		ESTs
780	4789	AI058889	General		ESTs
781	8221	AI059061	General		ESTs
782	10159	AI059147	d		EST
783	8245	AI059154	b		ESTs, Weakly similar to unnamed
					protein product [ H. sapiens ]
784	8283	AI059290	n		ESTs
785	8314	AI059386	g, General		ESTs
786	10200	AI059444	i		ESTs
787	8347	AI059519	s		ESTs, Weakly similar to EGF RAT
					PRO-EPIDERMAL GROWTH
					FACTOR PRECURSOR
					[ R. norvegicus ]
788	18359	AI059675	n		Rattus norvegicus transitional
					endoplasmic reticulum ATPase
					mRNA, complete cds
789	10281	AI059947	b, t		EST
790	8494	AI059968	aa		ESTs
791	8495	AI059971	General		ESTs, Weakly similar to TNRC
					MOUSE LYMPHOTOXIN-BETA
					RECEPTOR PRECURSOR
					[ M. musculus ]
792	8496	AI059974	General		ESTs, Moderately similar to KIAA0978
					protein [ H. sapiens ]
793	10289	AI060053	i		ESTs, Weakly similar to CGI-142
					hypothetical protein [ H. sapiens ]
794	8548	AI060176	k		ESTs
795	8565	AI060236	t		EST
796	18322	AI060279	i, y, z		ESTs
797	8745	AI069939	r		ESTs
798	8785	AI070067	o		ESTs, Highly similar to rer
					[ M. musculus ]
799	17506	AI070068	cc		ESTs, Weakly similar to 2104282A
					Gadd45 gene [ R. norvegicus ]
800	9067	AI070087	General		ESTs, Weakly similar to NUCL RAT
					NUCLEOLIN [ R. norvegicus ]
801	3551	AI070122	e		ESTs, Moderately similar to CGI-97
					protein [ H. sapiens ]
802	4967	AI070179	k		ESTs, Moderately similar to GLMB
					RAT GLIA MATURATION FACTOR
					BETA [ R. norvegicus ]
803	18	AI070195	General		ESTs, Moderately similar to AF132954
					1 CGI-20 protein [ H. sapiens ]
804	24197	AI070314	General		ESTs, Moderately similar to
					ARVC_HUMAN ARMADILLO
					REPEAT PROTEIN DELETED IN
					VELO-CARDIO-FACIAL SYNDROME
					[ H. sapiens ]
805	8869	AI070330	r		ESTs
806	8874	AI070336	b, cc		ESTs
807	10417	AI070410	m		ESTs
808	8901	AI070419	aa		ESTs, Moderately similar to T08664
					Toll protein-like receptor
					DKFZp547I0610.1 [ H. sapiens ]
809	14424	AI070421	l, p,		ESTs
			General
810	10434	AI070497	General		ESTs
811	8927	AI070523	v		ESTs
812	8946	AI070611	q		ESTs
813	8950	AI070621	w		ESTs
814	8972	AI070673	General		ESTs
815	8981	AI070715	bb		EST
816	26184	AI070784	i, l
817	3007	AI070824	w		ESTs, Weakly similar to hypothetical
					protein [ H. sapiens ]
818	8999	AI070839	p		ESTs
819	10477	AI070868	e, f	bone morphogenetic protein	bone morphogenetic protein 1
				1 (procollagen C-proetinase)	(procollagen C-proetinase)
820	24301	AI070911	k		ESTs
821	8721	AI071024	General		EST
822	9212	AI071098	x		ESTs
823	1831	AI071137	c		Rat mRNA for cdc25B, complete cds
824	11005	AI071139	r		EST
825	9104	AI071173	j, m		ESTs, Highly similar to
					HETEROGENEOUS NUCLEAR
					RIBONUCLEOPROTEIN G
					[ M. musculus ]
826	9583	AI071185	General		ESTs
827	9644	AI071410	c		ESTs
828	16058	AI071490	General	HHs: serine	ESTs, Highly similar to JC5180 serine
				palmitoyltransferase, long	C-palmitoyltransferase [ M. musculus ]
				chain base subunit 2
829	11057	AI071509	f, o		ESTs
831	5695	AI071566	bb		ESTs, Weakly similar to SYBSR
					threonine synthase (EC 4.2.99.2) -
					yeast (Saccharomyces cerevisiae)
					[ S. cerevisiae ]
832	9671	AI071568	w		EST
833	22929	AI071578	General		ESTs, Moderately similar to
					NEURONAL PROTEIN 3.1
					[ M. musculus ]
834	9673	AI071581	General		ESTs
835	9699	AI071646	General		ESTs
837	9799	AI072008	q, y, z		ESTs
838	9808	AI072050	d		ESTs
839	22796	AI072213	General		ESTs
840	9271	AI072405	v		ESTs
841	10869	AI072425	w		ESTs
842	21797	AI072439	General		ESTs, Weakly similar to S70484 RS43
					protein - rat (fragment) [ R. norvegicus ]
843	9306	AI072521	r		ESTs
844	9312	AI072550	j		ESTs
845	10893	AI072559	x		EST
846	1501	AI072634	cc, General		Rattus norvegicus cytokeratin-18
					mRNA, partial cds
847	6548	AI072658	General		ESTs
848	9363	AI072695	d		ESTs, Highly similar to JE0170 dnaJ
					heat shock protein MCG18 - mouse
					[ M. musculus ]
850	9409	AI072841	n		ESTs, Moderately similar to LMG2
					MOUSE LAMININ GAMMA-2 CHAIN
					PRECURSOR [ M. musculus ]
851	9410	AI072842	w		ESTs
852	9468	AI073021	General		ESTs
853	9518	AI073223	f		EST
854	11183	AI100768	t	HHs: carbonic anhydrase VIII	ESTs, Weakly similar to CAH2 RAT
					CARBONIC ANHYDRASE II
					[ R. norvegicus ]
855	9190	AI100835	e		ESTs
856	2029	AI100842	p		ESTs
857	5687	AI101006	e		ESTs
858	15192	AI101099	g, cc		Rat metallothionein-2 and
					metallothionein-1 genes, complete cds
859	17399	AI101157	o		ESTs, Highly similar to ATPK MOUSE
					ATP SYNTHASE F CHAIN,
					MITOCHONDRIAL [ M. musculus ]
860	9339	AI101160	l, m, o		ESTs, Weakly similar to S46930
					teg292 protein - mouse [ M. musculus ]
861	6321	AI101256	General		ESTs, Weakly similar to AIF-C1
					[ R. norvegicus ]
862	5421	AI101270	c		ESTs, Highly similar to GDIS MOUSE
					RHO GDP-DISSOCIATION
					INHIBITOR 2 [ M. musculus ]
863	11910	AI101323	General		ESTs, Highly similar to ERM_HUMAN
					ETS-RELATED PROTEIN ERM
					[ H. sapiens ]
864	23140	AI101608	e		ESTs
865	4119	AI101901	General		ESTs
866	16324	AI102009	b		ESTs, Weakly similar to TRBP
					MOUSE PROTAMINE-1 RNA
					BINDING PROTEIN [ M. musculus ]
867	18642	AI102023	o		ESTs, Moderately similar to unknown
					[ H. sapiens ]
868	19373	AI102044	a	Drosophila polarity gene	Rattus norvegicus mRNA for beta-
				(frizzled) homologue	carotene 15,15′-dioxygenase,
					complete cds
869	7051	AI102055	h		Rattus norvegicus clone ZG52 mRNA
					sequence
870	6544	AI102064	c		ESTs, Weakly similar to AF147718 1
					glycine decarboxylase [ R. norvegicus ]
871	10227	AI102248	w		ESTs
872	23849	AI102318	e, q		ESTs
873	11954	AI102505	g, j, s	HMm: cytochrome c oxidase,	Rattus norvegicus liver cytochrome c
				subunit VIIIa	oxidase subunit VIII (COX-VIII)
					mRNA, 3′ end of cds
874	2125	AI102519	c, k		ESTs, Moderately similar to DAP12
					[ M. musculus ]
875	5967	AI102520	y		ESTs, Moderately similar to AF161588
					1 GABA-A receptor-associated protein
					[ R. norvegicus ]
875	5969	AI102520	p, w		ESTs, Moderately similar to AF161588
					1 GABA-A receptor-associated protein
					[ R. norvegicus ]
876	11563	AI102560	General		ESTs
877	15190	AI102562	b, g, n, p, v		Rat metallothionein-i (mt-1) mrna
878	19769	AI102570	bb		EST, Weakly similar to A60716
					somatotropin intron-related protein
					RDE.25 - rat [ R. norvegicus ]
879	22487	AI102578	General		ESTs, Highly similar to I49523 Mouse
					primary response gene B94 mRNA,
					3′end - mouse [ M. musculus ]
880	19011	AI102618	General		ESTs
881	23837	AI102620	q, t		ESTs
882	23538	AI102727	g, General	solute carrier family 20	solute carrier family 20 (phosphate
				(phosphate transporter),	transporter), member 1
				member 1
883	17234	AI102741	c	Tissue inhibitor of	Tissue inhibitor of metalloproteinase 3
				metalloproteinase 3
884	5891	AI102745	k		ESTs
885	6796	AI102753	General		ESTs
886	8837	AI102849	o, p		ESTs
887	15861	AI102868	i		ESTs, Weakly similar to
					phosphoserine aminotransferase
					[ H. sapiens ]
888	3533	AI102877	g		ESTs
889	13222	AI102977	General		ESTs, Highly similar to PCAF
					associated factor 65 beta [ H. sapiens ]
890	6806	AI103018	o, u		ESTs
891	10659	AI103059	w, cc,		ESTs
			General
892	17400	AI103097	e		ESTs, Highly similar to ATPK MOUSE
					ATP SYNTHASE F CHAIN,
					MITOCHONDRIAL [ M. musculus ]
893	3584	AI103106	x, aa		ESTs
894	13298	AI103143	r		ESTs
895	15981	AI103150	i, x		ESTs, Weakly similar to
					UBC2_HUMAN UBIQUITIN-
					CONJUGATING ENZYME E2-17 KD
					[ R. norvegicus ]
896	3475	AI103245	w		ESTs, Highly similar to AF151893 1
					CGI-135 protein [ H. sapiens ]
898	23619	AI103314	p		ESTs
899	24181	AI103320	e		ESTs, Moderately similar to T26785
					hypothetical protein Y40B1B.7 -
					Caenorhabditis elegans [ C. elegans ]
901	4355	AI103410	General		ESTs
902	7622	AI103472	General		ESTs
903	20918	AI103552	n		ESTs
904	21579	AI103572	General		ESTs
905	2222	AI103631	o		ESTs, Highly similar to RIE2
					[ M. musculus ]
906	2752	AI103641	e		ESTs, Highly similar to sarcosine
					dehydrogenase [ R. norvegicus ]
907	4856	AI103708	i		ESTs
908	8990	AI103719	l, m, y, z
909	15942	AI103738	r		ESTs
910	22885	AI103828	e, General		ESTs
911	15853	AI103841	x	Complement component 4	Complement component 4
912	15050	AI103911	j, y	HHs: ubiquinol-cytochrome c	Rat Rieske iron-sulfur protein mRNA,
				reductase, Rieske iron-sulfur	complete cds
				polypeptide 1
913	12376	AI103939	u		ESTs
914	22271	AI103947	o, y		ESTs, Weakly similar to AF151109 1
					putative BRCA1-interacting protein
					[ H. sapiens ]
915	20833	AI104035	f, q	HMm: RIKEN cDNA	ESTs, Highly similar to COXG
				2010000G05 gene	MOUSE CYTOCHROME C OXIDASE
					POLYPEPTIDE VIB [ M. musculus ]
916	7010	AI104099	w		ESTs
917	22101	AI104251	General		ESTs
918	22833	AI104258	General		ESTs
919	22211	AI104279	g, m		ESTs, Highly similar to translation
					initiation factor elF6 [ M. musculus ]
920	10720	AI104296	l		ESTs
921	15416	AI104340	i		ESTs
922	10991	AI104342	a		ESTs
923	18831	AI104357	p		ESTs, Highly similar to ATRTC actin
					beta - rat [ R. norvegicus ]
924	7223	AI104373	e		ESTs
925	23574	AI104520	e, g, s	Cytochrome c oxidase	Cytochrome c oxidase subunit VIa
				subunit VIa (liver)	(liver)
926	18509	AI104528	q		ESTs, Weakly similar to
					NADH: ubiquinone oxidoreductase B17
					subunit [ H. sapiens ]
927	11680	AI104605	v		ESTs
928	12342	AI104658	w		ESTs, Weakly similar to RENAL
					TRANSCRIPTION FACTOR KID-1
					[ R. norvegicus ]
929	23689	AI104685	r		Rat mitochondrial succinyl-CoA
					synthetase alpha subunit (cytoplasmic
					precursor) mRNA, complete cds
930	15377	AI104821	o, cc		ESTs, Moderately similar to T50611
					hypothetical protein
					DKFZp434H2035.1 [ H. sapiens ]
931	22957	AI104897	General		ESTs, Moderately similar to
					meningioma-expressed antigen 11
					[ H. sapiens ]
932	18451	AI104953	o, s	HHs: ATP synthase, H+	Rattus norvegicus delta subunit of
				transporting, mitochondrial	F1F0 ATPase gene, complete cds
				F1 complex, delta subunit
933	24375	AI104979	n, General		ESTs, Moderately similar to nucleolar
					protein p40 [ H. sapiens ]
934	18278	AI105080	bb		ESTs, Moderately similar to
					SCOT_HUMAN SUCCINYL-COA: 3-
					KETOACID-COENZYME A
					TRANSFERASE PRECURSOR
					[ H. sapiens ]
935	2196	AI105243	g		ESTs
936	5199	AI105272	bb,		ESTs, Weakly similar to T21641
			General		hypothetical protein F32B6.2 -
					Caenorhabditis elegans [ C. elegans ]
937	12901	AI105301	o, s		ESTs
938	7700	AI105383	cc,		ESTs, Weakly similar to T19707
			General		hypothetical protein C34C6.5 -
					Caenorhabditis elegans [ C. elegans ]
939	13343	AI105398	u		ESTs
940	22931	AI105417	e, General		ESTs, Moderately similar to
					NEURONAL PROTEIN 3.1
					[ M. musculus ]
941	23596	AI105435	bb	HMm: glutaryl-Coenzyme A	ESTs, Highly similar to GCDH
				dehydrogenase	MOUSE GLUTARYL-COA
					DEHYDROGENASE PRECURSOR
					[ M. musculus ]
942	15893	AI105465	o		ESTs, Moderately similar to
					DHSD_HUMAN SUCCINATE
					DEHYDROGENASE [ H. sapiens ]
943	12660	AI111492	c		ESTs
944	4479	AI111599	General		ESTs
945	24211	AI111853	k		ESTs, Highly similar to H33_HUMAN
					HISTONE H3.3 [ R. norvegicus ]
946	2539	AI111960	r		ESTs, Weakly similar to FKB5
					MOUSE 51 KDA FK506-BINDING
					PROTEIN [ M. musculus ]
947	5729	AI111990	k		EGF-CONTAINING FIBULIN-LIKE
					EXTRACELLULAR MATRIX
					PROTEIN 1 PRECURSOR (FIBULIN-
					3) (FIBL-3) (T16 PROTEIN)
					[ R. norvegicus ]
948	4049	AI112012	i, q, u,		Rattus norvegicus osteoactivin mRNA,
			General		complete cds
949	12908	AI112043	i		ESTs
950	20041	AI112161	t		ESTs
951	12937	AI112462	General		ESTs
952	3713	AI112571	b		ESTs
953	12921	AI112636	General		ESTs, Moderately similar to
					UDP_HUMAN URIDINE
					PHOSPHORYLASE [ H. sapiens ]
954	12965	AI112926	General		ESTs
955	7499	AI112986	General		ESTs
956	4969	AI113008	r		ESTs, Moderately similar to
					megakaryocyte stimulating factor
					[ H. sapiens ]
957	11817	AI136295	f		ESTs, Highly similar to BC-2 protein
					[ H. sapiens ]
959	11165	AI136372	c		ESTs, Weakly similar to JC4975
					plexin 2 precursor - mouse
					[ M. musculus ]
960	4045	AI136460	cc		ESTs
961	12782	AI136493	k		ESTs
962	6850	AI136665	h	ecto-apyrase	ecto-apyrase
963	20920	AI136891	p, v	butyrate response factor 1	butyrate response factor 1
964	6552	AI137062	o		ESTs, Highly similar to 6.2 kd protein
					[ H. sapiens ]
965	22722	AI137211	i		ESTs
966	13111	AI137224	o, General		ESTs, Highly similar to oxysterol-
					binding protein [ M. musculus ]
967	15969	AI137302	e		ESTs
968	14349	AI137303	d		ESTs
969	9166	AI137406	General		ESTs
970	9525	AI137516	r		ESTs, Weakly similar to ZF37_RAT
					ZINC FINGER PROTEIN 37 (ZFP-37)
					[ R. norvegicus ]
971	6638	AI137579	General		ESTs
972	7414	AI137586	General		ESTs, Highly similar to IMB3_HUMAN
					IMPORTIN BETA-3 SUBUNIT
					[ H. sapiens ]
973	11321	AI137752	z		ESTs
974	23473	AI137932	l		ESTs
975	13158	AI138024	i		ESTs
976	13467	AI138034	cc	UDP-glucose: ceramide	UDP-glucose: ceramide
				glycosyltransferase	glycosyltransferase
977	11377	AI138105	y		ESTs
978	6790	AI144801	d, h		ESTs
979	6506	AI144919	j, l, y		ESTs
980	8027	AI144958	i		ESTs
982	14458	AI145095	General		ESTs
983	7476	AI145202	g		ESTs
984	17545	AI145384	e		ESTs, ESTs, Weakly similar to GTP-
					binding protein [ H. sapiens ]
985	17479	AI145385	r		ESTs
986	4194	AI145387	r		ESTs
987	8634	AI145722	g		ESTs, Weakly similar to T31511
					hypothetical protein Y116A8C.9 -
					Caenorhabditis elegans [ C. elegans ]
988	8339	AI145761	y, General		ESTs, Weakly similar to T21659
					hypothetical protein F32D8.4 -
					Caenorhabditis elegans [ C. elegans ]
989	2059	AI46005	h, General		ESTs, Highly similar to pseudouridine
					synthase 1 [ M. musculus ]
990	23224	AI146033	o		Rattus norvegicus small zinc finger-
					like protein (TIM9a) mRNA, partial cds
991	5232	AI168942	bb	branched chain keto acid	branched chain keto acid
				dehydrogenase E1, beta	dehydrogenase E1, beta polypeptide
				polypeptide
992	18472	AI168975	u		ESTs
992	18473	AI168975	u		ESTs
993	13235	AI169020	r		ESTs
994	11618	AI169115	o, y,		ESTs
			General
995	17386	AI169144	o		ESTs, Weakly similar to T23206
					hypothetical protein K01H12.1 -
					Caenorhabditis elegans [ C. elegans ]
996	10984	AI169156	o, u		ESTs, Weakly similar to HP33
					[ R. norvegicus ]
997	8205	AI169176	e		ESTs
998	12979	AI169177	e		ESTs, Highly similar to RADIATION-
					INDUCIBLE IMMEDIATE-EARLY
					GENE IEX-1 [ M. musculus ]
999	2607	AI169211	c		ESTs, Highly similar to A47318 RNA-
					binding protein Raly - mouse
					[ M. musculus ]
1000	22661	AI169265	s, z	ATPase, H+ transporting,	ATPase, H+ transporting, lysosomal
				lysosomal (vacuolar proton	(vacuolar proton pump), subunit 1
				pump), subun
1001	13239	AI169278	g, j, l, y, z		ESTs
1002	24162	AI169279	m		ESTS
1003	16879	AI169284	o		ESTs, Highly similar to Y069_HUMAN
					HYPOTHETICAL PROTEIN KIAA0069
					[ H. sapiens ]
1004	24213	AI169289	p		ESTs, Highly similar to H33_HUMAN
					HISTONE H3.3 [ R. norvegicus ]
1005	13240	AI169311	cc		ESTs
1006	5931	AI169324	b		ESTs
1007	20891	AI169337	d		ESTs, Highly similar to CGI-117
					protein [ H. sapiens ]
1008	11979	AI169365	cc		ESTs
1009	10947	AI169372	s	arachidonic acid	arachidonic acid epoxygenase
				epoxygenase
1010	20697	AI169494	o, u		ESTs
1011	8234	AI169517	z		ESTs
1012	18343	AI169648	o		ESTs
1013	10839	AI169655	l, m		ESTs
1014	24146	AI169668	j, l		ESTs, Weakly similar to hypothetical
					protein [ H. sapiens ]
1015	22575	AI169728	r		ESTs, Moderately similar to T47184
					hypothetical protein
					DKFZp434F1526.1 [ H. sapiens ]
1016	804	AI169756	cc		ESTs, Highly similar to GENE 33
					POLYPEPTIDE [ R. norvegicus ]
1017	8213	AI169883	p	ferritin light chain 1	ferritin light chain 1
1018	3916	AI169947	i, bb		ESTs
1019	3733	AI170053	u, General		ESTs
1020	14179	AI170224	cc		ESTs
1021	11406	AI170263	r		ESTs, Moderately similar to class II
					cytokine receptor 4 [ M. musculus ]
1022	3547	AI170279	General		ESTs, Weakly similar to ZNT1 RAT
					ZINC TRANSPORTER 1
					[ R. norvegicus ]
1023	11524	AI170340	j, y, z		ESTs, Weakly similar to CL36 RAT
					LIM DOMAIN PROTEIN CLP-36
					[ R. norvegicus ]
1024	2729	AI170363	e, i		ESTs
1025	18811	AI170525	i		ESTs
1026	22524	AI170542	h		ESTs
1027	24048	AI170570	a, g		ESTs, Highly similar to CGI-10 protein
					[ H. sapiens ]
1028	5968	AI170692	y, aa		ESTs, Moderately similar to AF161588
					1 GABA-A receptor-associated protein
					[ R. norvegicus ]
1029	9757	AI170693	b		ESTs
1030	18905	AI170770	e, s		ESTs, Highly similar to NADH-
					ubiquinone oxidoreductase NDUFS2
					subunit [ H. sapiens ]
1031	16170	AI170894	i		ESTs, Moderately similar to
					adipophilin [ H. sapiens ]
1032	7089	AI171185	c	Hyaluronan mediated motility	Hyaluronan mediated motility receptor
				receptor (RHAMM)	(RHAMM)
1033	17591	AI171354	b		ESTs
1034	13285	AI171361	h		ESTs, Weakly similar to AIF-C1
					[ R. norvegicus ]
1035	4428	AI171362	a	HHs: NADH dehydrogenase	ESTs, Moderately similar to
				(ubiquinone) Fe—S protein 1	NUAM_HUMAN NADH-UBIQUINONE
				(75 kD) (NADH-coenzyme Q	OXIDOREDUCTASE 75 KD SUBUNIT
				reductase)	PRECURSOR [ H. sapiens ]
1036	18126	AI171369	w		ESTs, Highly similar to S16788
					probable reverse transcriptase - rat
					[ R. norvegicus ]
1037	23253	AI171448	o		ESTs, Moderately similar to 68MP
					MOUSE 6.8 KD MITOCHONDRIAL
					PROTEOLIPID [ M. musculus ]
1038	4584	AI171492	m,		ESTs
			General
1039	11158	AI171542	r, s		ESTs, Moderately similar to
					NADH: ubiquinone oxidoreductase B22
					subunit [ H. sapiens ]
1040	15345	AI171587	l		ESTs
1041	21183	AI171676	k		ESTs
1042	8215	AI171692	i	ferritin light chain 1	Rattus norvegicus kynurenine
					aminotransferase/glutamine
					transaminase K (Kat) gene, complete
					cds, ferritin light chain 1
1043	11437	AI171794	i		ESTs
1044	2625	AI171800	cc		ESTs
1045	23579	AI171802	v		ESTs
1046	11708	AI171807	l, t		ESTs
1047	17204	AI171844	s, y, z	HMm: RIKEN cDNA	Rattus norvegicus F1-ATPase epsilon
				2410043G19 gene	subunit mRNA, nuclear gene encoding
					mitochondrial protein, complete cds
1048	4420	AI171916	m		ESTs
1049	3266	AI171948	l, m		ESTs, Highly similar to T08675
					hypothetical protein
					DKFZp564F0522.1 [ H. sapiens ]
1050	19012	AI172056	t		ESTs
1051	11205	AI172057	a, q, bb		ESTs
1052	6057	AI172102	b		ESTs, Weakly similar to T33238
					hypothetical protein T10H9.3 -
					Caenorhabditis elegans [ C. elegans ]
1053	19128	AI172103	m		ESTs
1054	15673	AI172107	z		Rat mRNA for 5E5 antigen, complete
					cds
1055	6630	AI172184	n		ESTs
1056	11968	AI172208	bb		ESTs, Weakly similar to FETA RAT
					ALPHA-FETOPROTEIN
					PRECURSOR [ R. norvegicus ]
1057	6974	AI172263	l, m		ESTs
1058	23313	AI172271	d		ESTs
1059	2140	AI172272	General		ESTs, Moderately similar to A53004
					transcription elongation factor S-II - rat
					[ R. norvegicus ]
1060	15382	AI172302	l, p,		ESTs, Weakly similar to S43056
			General		hypothetical protein - mouse
					[ M. musculus ]
1061	18689	AI172329	l		ESTs
1062	17887	AI172414	o		Rattus norvegicus apoptosis-
					regulating basic protein mRNA,
					complete cds
1063	3042	AI172447	General		ESTs, Highly similar to A44437
					regenerating liver inhibitory factor
					RL/IF-1 - rat [ R. norvegicus ]
1064	17291	AI172491	bb	HMm: isocitrate	ESTs, Weakly similar to IDHC RAT
				dehydrogenase 2 (NADP+),	ISOCITRATE DEHYDROGENASE
				mitochondrial	[ R. norvegicus ]
1065	26222	AI172506	p
1066	13095	AI172595	r		ESTs
1067	8795	AI172618	General		ESTs
1068	6454	AI175342	j, l, m, y		ESTs, Weakly similar to T31067 BIR
					repeat containing ubiquitin-
					conjugating enzyme BRUCE - mouse
					[ M. musculus ]
1070	4445	AI175466	x		ESTs, Highly similar to RRAS MOUSE
					RAS-RELATED PROTEIN R-RAS
					[ M. musculus ]
1071	3418	AI175475	m		ESTs, Highly similar to NHPX RAT
					NHP2/RS6 FAMILY PROTEIN
					YEL026W HOMOLOG [ R. norvegicus ]
1072	18507	AI175551	bb		ESTs, Moderately similar to AF145050
					1 translation elongation factor 1-delta
					subunit [ R. norvegicus ]
1073	10217	AI175628	w		ESTs
1074	7262	AI175833	j, m, x		ESTs
1075	19004	AI175875	r		ESTs
1076	22352	AI175959	l, General		ESTs
1077	7022	AI176041	h, n		ESTs, Highly similar to pirin
					[ H. sapiens ]
1078	21467	AI176061	t		ESTs, Weakly similar to tazarotene-
					induced gene 2 [ H. sapiens ]
1079	18581	AI176160	General		ESTs
1080	14159	AI176169	g		ESTs
1081	21742	AI176172	w		ESTs
1082	10182	AI176185	v		ESTs, Highly similar to P55-C-FOS
					PROTO-ONCOGENE PROTEIN
					[ R. norvegicus ]
1083	22765	AI176265	General		ESTs
1084	6905	AI176275	a		ESTs, Weakly similar to GSHH RAT
					PHOSPHOLIPID HYDROPEROXIDE
					GLUTATHIONE PEROXIDASE
					[ R. norvegicus ]
1085	12999	AI176276	cc		UAP1_HUMAN UDP-N-
					ACETYLHEXOSAMINE
					PYROPHOSPHORYLASE [ H. sapiens ]
1086	16438	AI176294	e		ESTs, Highly similar to
					SMD2_HUMAN SMALL NUCLEAR
					RIBONUCLEOPROTEIN SM D2
					[ H. sapiens ]
1087	21130	AI176298	y		ESTs
1088	3014	AI176362	e		ESTs
1089	15015	AI176363	r		ESTs
1090	19006	AI176393	x		ESTs
1091	20001	AI176396	o		ESTs, Moderately similar to QPS1
					[ H. sapiens ]
1092	12174	AI176435	j, m		ESTs
1093	15191	AI176456	b, o, t, v, cc		Rat metallothionein-2 and
					metallothionein-1 genes, complete cds
1094	24236	AI176473	d, General		ESTs
1095	16518	AI176546	v		ESTs, Moderately similar to HS9B
					RAT HEAT SHOCK PROTEIN HSP
					90-BETA [ R. norvegicus ]
1096	2161	AI176592	General		ESTs
1097	12436	AI176610	General		ESTs, Weakly similar to S63220
					probable membrane protein YNL247w -
					yeast (Saccharomyces cerevisiae)
					[ S. cerevisiae ]
1098	2536	AI176616	l, v,		ESTs
			General
1099	18525	AI176792	u		ESTs
1100	23449	AI176828	g		ESTs
1101	23299	AI176839	General		ESTs
1102	3580	AI176848	e		ESTs
1103	22103	AI176849	d, General		ESTs
1104	16036	AI176855	f		ESTs
1105	15588	AI176916	General		ESTs, Highly similar to
					phosphomannomutase Sec53p
					homolog [ M. musculus ]
1106	16917	AI176951	t		ESTs
1107	16124	AI176963	cc		Rattus norvegicus transcription factor
					MRG1 mRNA, complete cds
1108	15146	AI176969	b, General		ESTs
1109	5786	AI177058	f		ESTs, Weakly similar to PSE-binding
					factor PTF delta subunit [ H. sapiens ]
1110	2852	AI177059	c		ESTs
1112	3156	AI177092	g		ESTs, Highly similar to AF139894 1
					RNA-binding protein alpha-CP1
					[ M. musculus ]
1113	14384	AI177096	a	HMm: adenine	Rat adenine
				phosphoribosyl transferase	phosphoribosyltransferase (APRT)
					gene, complete cds
1114	13310	AI177119	General		ESTs, Weakly similar to C1QB RAT
					COMPLEMENT C1Q
					SUBCOMPONENT, B CHAIN
					PRECURSOR [ R. norvegicus ]
1115	24049	AI177341	g, p, s, u		ESTs, Highly similar to CGI-10 protein
					[ H. sapiens ]
1116	15964	AI177360	o, General		ESTs
1117	14989	AI177366	u	Integrin, beta 1	Integrin, beta 1
1118	7975	AI177374	aa		ESTs
1119	3006	AI177395	k		Rattus norvegicus substrate binding
					subunit of type II 5′-deiodinase D2p29
					mRNA, complete cds
1120	17570	AI177683	r		Rattus norvegicus mRNA for hnRNP
					protein, partial
1121	9521	AI177706	b		ESTs
1122	14425	AI177755	g, General		ESTs
1123	10611	AI177790	j, m		ESTs
1124	5356	AI177813	cc		ESTs, Moderately similar to S27962
					modulator recognition factor 1
					[ H. sapiens ]
1125	11791	AI177843	General		ESTs, Highly similar to SAS_HUMAN
					SARCOMA AMPLIFIED SEQUENCE
					[ H. sapiens ]
1126	14484	AI177867	General		ESTs, Weakly similar to putative eps
					protein [ R. norvegicus ]
1127	5780	AI177869	General		ESTs, Weakly similar to DRAL
					[ R. norvegicus ]
1128	19184	AI178025	General		ESTs, Highly similar to TGIF MOUSE
					5′-TG-3′ INTERACTING FACTOR
					[ M. musculus ]
1129	6059	AI178245	c, General		ESTs, Moderately similar to C17orf1
					protein [ H. sapiens ]
1130	23248	AI178267	y		ESTs, Weakly similar to hypothetical
					protein [ H. sapiens ]
1131	4073	AI178272	o		ESTs, Weakly similar to
					YAE6_YEAST HYPOTHETICAL 13.4 KD
					PROTEIN IN ACS1-GCV3
					INTERGENIC REGION [ S. cerevisiae ]
1132	7838	AI178291	e		ESTs
1133	18996	AI178326	y		ESTs
1134	22488	AI178392	b		ESTs, Highly similar to I49523 Mouse
					primary response gene B94 mRNA,
					3′end - mouse [ M. musculus ]
1135	18800	AI178504	n, p, aa		ESTs
1136	22197	AI178527	g, General		ESTs
1137	3401	AI178684	bb		ESTs, Highly similar to MCM3
					MOUSE DNA REPLICATION
					LICENSING FACTOR MCM3
					[ M. musculus ]
1138	17713	AI178700	m		ESTs
1139	14874	AI178735	e		ESTs
1140	23567	AI178746	v, General		ESTs
1141	18907	AI178971	c		Rattus norvegicus alpha-globin (GloA)
					gene, complete cds
1142	20991	AI178979	i		ESTs
1143	5887	AI179099	q, t		ESTs, Moderately similar to Vanin-1
					[ M. musculus ]
1144	8477	AI179167	b, e,		ESTs
			General
1145	3348	AI179288	u, v		ESTs
1146	13608	AI179314	e		ESTs
1147	8849	AI179315	g, p		ESTs
1148	13611	AI179378	v, General		Rattus norvegicus mRNA for prostasin
					precursor, complete cds
1149	15438	AI179399	m, x	collagen type V, alpha 2	collagen type V, alpha 2
1150	13614	AI179407	e, t,		ESTs, Moderately similar to RB17
			General		MOUSE RAS-RELATED PROTEIN
					RAB-17 [ M. musculus ]
1151	15042	AI179422	b, General		ESTs
1152	2768	AI179481	i, General		ESTs
1153	24041	AI179580	b, i		ESTs
1154	19822	AI179599	o, General		R. norvegicus mRNA for ras-related
					GTPase Rab29
1155	23270	AI179601	q, General		ESTs
1156	5901	AI179605	e		ESTs
1157	16081	AI179610	g, i, p	Heme oxygenase	Heme oxygenase
1158	14564	AI179717	k		ESTs
1159	7918	AI179750	General		ESTs
1160	6647	AI179795	g		ESTs
1161	9097	AI179875	o, General	hypothetical protein	hypothetical protein LOC56728
				LOC56728
1162	23989	AI179953	a		ESTs, Highly similar to GAP
					JUNCTION BETA-2 PROTEIN
					[ R. norvegicus ]
1163	12899	AI179967	b		ESTs
1164	1687	AI179971	c	Hemoglobin, alpha 1	Hemoglobin, alpha 1
1165	22569	AI179979	General		ESTs
1166	23514	AI179986	o, General	HHs: phosphoserine	ESTs, Highly similar to L-3-
				phosphatase	phosphoserine phosphatase
					[ H. sapiens ]
1167	15892	AI179988	c, General		ESTs
1168	12402	AI180004	g		ESTs, Highly similar to Unknown
					[ H. sapiens ]
1169	5443	AI180165	General		ESTs, Moderately similar to testis
					specific DNAj-homolog [ M. musculus ]
1170	5481	AI180170	General		ESTs, Highly similar to A Chain A,
					The Crystal Structure Of Human
					Eukaryotic Release Factor Erf1-
					Mechanism Of Stop Codon
					Recognition And Peptidyl-Tma
					Hydrolysis [ H. sapiens ]
1171	24028	AI180239	i		ESTs
1172	17089	AI180281	g		ESTs, Moderately similar to JC4978
					oxidative stress protein A170 - mouse
					[ M. musculus ]
1173	3701	AI180306	aa		ESTs, Moderately similar to
					Y273_HUMAN HYPOTHETICAL
					PROTEIN KIAA0273 [ H. sapiens ]
1174	3352	AI180334	m		ESTs
1175	24368	AI180392	l, m		ESTs, Highly similar to AF114169 1
					nucleotide-binding protein short form
					[ M. musculus ]
1176	14337	AI180414	c		ESTs, Moderately similar to SPA1
					MOUSE GTPASE-ACTIVATING
					PROTEIN SPA-1 [ M. musculus ]
1177	19080	AI227647	j, y, z		Rattus norvegicus chemokine CX3C
					mRNA, complete cds
1178	22838	AI227667	aa		ESTs
1179	6765	AI227761	i, General		ESTs, Highly similar to T00367
					hypothetical protein KIAA0665
					[ H. sapiens ]
1180	24054	AI227867	General		ESTs, Weakly similar to AF187065 1
					p75NTR-associated cell death
					executor [ R. norvegicus ]
1181	7324	AI227885	i		ESTs
1182	23898	AI227987	d		ESTs
1183	1651	AI228068	n, w	Peptidylglycine alpha-	Peptidylglycine alpha-amidating
				amidating monooxygenase	monooxygenase
1184	14237	AI228128	e		EST
1185	14242	AI228197	General		ESTs, Weakly similar to
					C21I_HUMAN PUTATIVE PROTEIN
					C21ORF18 [ H. sapiens ]
1186	16913	AI228236	o		ESTs
1187	22915	AI228299	r		ESTs, Highly similar to p97
					homologous protein [ H. sapiens ]
1188	8917	AI228301	General		ESTs
1189	15879	AI228313	r, General		ESTs
1190	13727	AI228326	o, General		ESTs, Weakly similar to
					AFG1_YEAST AFG1 PROTEIN
					[ S. cerevisiae ]
1191	6102	AI228335	General		ESTs
1192	13730	AI228356	a		ESTs, Weakly similar to S70642
					ubiquitin ligase Nedd4 - rat
					[ R. norvegicus ]
1193	13745	AI228494	b, cc		EST
1194	4217	AI228587	s		ESTs, Weakly similar to
					M172_HUMAN MEMBRANE
					COMPONENT, CHROMOSOME 17,
					SURFACE MARKER 2 [ H. sapiens ]
1195	16053	AI228596	cc		ESTs, Weakly similar to T16757
					hypothetical protein R144.3 -
					Caenorhabditis elegans [ C. elegans ]
1196	3557	AI228672	e		ESTs
1197	11605	AI228682	e		ESTs
1198	13203	AI228728	r		ESTs
1199	13771	AI228848	g		ESTs, Highly similar to protein
					inhibitor of activated STAT protein
					PIAS1 [ H. sapiens ]
1200	5918	AI229036	r		ESTs
1201	8235	AI229154	k		ESTs
1202	16203	AI229196	r	Vesicle-associated	Vesicle-associated membrane protein
				membrane protein	(synaptobrevin 2)
				(synaptobrevin 2)
1203	13826	AI229304	a		ESTs
1204	13144	AI229320	g		ESTs
1205	4640	AI229404	x, aa		ESTs
1206	23563	AI229421	l		ESTs, Moderately similar to MKK2
					MOUSE MAP KINASE-ACTIVATED
					PROTEIN KINASE 2 [ M. musculus ]
1207	15426	AI229497	s		ESTs, Moderately similar to NADH-
					ubiquinone oxidoreductase PDSW
					subunit [ H. sapiens ]
1208	15193	AI229508	bb		ESTs
1209	19243	AI229638	x		ESTs, Highly similar to KITH RAT
					THYMIDINE KINASE, CYTOSOLIC
					[ R. norvegicus ]
1210	23078	AI229647	p		ESTs
1211	3099	AI229680	o	HHs: NADH dehydrogenase	ESTs, Highly similar to
				(ubiquinone) Fe—S protein 3	NADH: ubiquinone oxidoreductase
				(30 kD) (NADH-coenzyme Q	NDUFS3 subunit [ H. sapiens ]
				reductase)
1212	19508	AI229698	bb		Sprague-Dawley D-beta-
					hydroxybutyrate dehydrogenase
					mRNA, complete cds
1213	13977	AI229707	x		Rattus norvegicus mRNA for class I
					beta-tubulin, complete cds
1214	23983	AI229708	v		ESTs, Moderately similar to
					NADC_HUMAN NICOTINATE-
					NUCLEOTIDE
					PYROPHOSPHORYLASE [ H. sapiens ]
1215	2688	AI229793	e		ESTs
1216	13874	AI229832	g		ESTs, Weakly similar to KIAA0859
					protein [ H. sapiens ]
1217	12587	AI229979	General		ESTs, Weakly similar to MOT2 RAT
					MONOCARBOXYLATE
					TRANSPORTER 2 [ R. norvegicus ]
1218	20591	AI229993	l, m		ESTs
1219	24042	AI230002	a, b, d,		ESTs
			General
1220	13880	AI230042	u		Rattus norvegicus mRNA for voltage-
					gated ca channel, complete cds
1221	17672	AI230074	d	HMm: NADH dehydrogenase	ESTs, Highly similar to NIMM MOUSE
				(ubiquinone) 1 alpha	NADH-UBIQUINONE
				subcomplex, 1	OXIDOREDUCTASE MWFE
					SUBUNIT [ M. musculus ]
1222	3652	AI230113	General		Rattus norvegicus hfb2 mRNA,
					complete cds
1223	18650	AI230121	aa		ESTs, Weakly similar to HS9B RAT
					HEAT SHOCK PROTEIN HSP 90-
					BETA [ R. norvegicus ]
1224	13025	AI230173	c		ESTs, Moderately similar to
					CHD3_HUMAN CHROMODOMAIN
					HELICASE-DNA-BINDING PROTEIN
					3 [ H. sapiens ]
1225	4280	AI230247	z	selenoprotein P, plasma, 1	selenoprotein P, plasma, 1
1226	18528	AI230284	General		ESTs
1227	7084	AI230362	p		ESTs, Moderately similar to T46458
					hypothetical protein DKFZp434M102.1
					[ H. sapiens ]
1228	20895	AI230549	b, n		ESTs
1229	12961	AI230554	General		ESTs
1230	15636	AI230616	r		Rattus norvegicus mRNA for galectin-
					2 related protein, complete cds
1231	4121	AI230647	j, m		ESTs
1232	14388	AI230702	General		ESTs, Highly similar to HN1
					[ M. musculus ]
1233	18529	AI230716	x, General		ESTs
1234	13618	AI230724	General		Rattus norvegicus phosphoinositide
					phosphatase SAC1 mRNA, complete
					cds
1235	8304	AI230746	cc		ESTs
1236	4731	AI230773	e		ESTs
1237	14430	AI230798	c, k, x		ESTs, Moderately similar to
					CDN3_HUMAN CYCLIN-
					DEPENDENT KINASE INHIBITOR 3
					[ H. sapiens ]
1238	16627	AI230822	bb	HHs: Alg5, S. cerevisiae,	ESTs, Highly similar to AF102850 1
				homolog of	dolichyl-phosphate beta-
					glucosyltransferase [ H. sapiens ]
1239	3125	AI231028	General		Rattus norvegicus mRNA for brain
					4.1(S), complete cds
1240	633	AI231127	k		ESTs
1241	20846	AI231140	p		ESTs, Highly similar to RL2B_HUMAN
					60S RIBOSOMAL PROTEIN L23A
					[ R. norvegicus ]
1242	6743	AI231219	d		ESTs
1244	26292	AI231391	k
1245	12343	AI231433	w		ESTs
1246	7337	AI231465	aa		ESTs
1247	16321	AI231506	General		ESTs
1248	8004	AI231532	j, l		ESTs, Highly similar to Z183_HUMAN
					ZINC FINGER PROTEIN 183
					[ H. sapiens ]
1249	15171	AI231792	g		ESTs, Moderately similar to BAG-
					family molecular chaperone regulator-
					3 [ H. sapiens ]
1250	6193	AI231797	i		ESTs
1252	14227	AI231999	u		ESTs, Moderately similar to tumor
					protein D53 [ M. musculus ]
1253	24501	AI232006	w, y, bb		Rattus norvegicus translation
					elongation factor 1-delta subunit
					mRNA, partial cds
1254	3434	AI232014	g, q, z, cc,		ESTs
			General
1255	19094	AI232021	n, General		ESTs, Highly similar to Human
					Translation Initiation Factor Eif1, Nmr,
					29 Structures [ H. sapiens ]
1256	14020	AI232076	u		ESTs
1257	6726	AI232157	d		ESTs
1258	11549	AI232174	l, m		ESTs
1259	23125	AI232266	j, s		ESTs
1260	2085	AI232270	bb		ESTs, Moderately similar to JC4914
					anti-sigma cross-reacting protein
					homolog I beta precursor [ H. sapiens ]
1261	2913	AI232272	o		ESTs, Weakly similar to T25417
					hypothetical protein T28D6.9 -
					Caenorhabditis elegans [ C. elegans ]
1262	14304	AI232281	g		ESTs, Weakly similar to KIAA0971
					protein [ H. sapiens ]
1263	15955	AI232294	u, bb,		ESTs
			General
1264	15122	AI232303	y		ESTs, Weakly similar to Sid1669p
					[ M. musculus ]
1265	4716	AI232313	y	purinergic receptor P2X,	purinergic receptor P2X, ligand-gated
				ligand-gated ion channel 4	ion channel 4
1266	15246	AI232332	t, u		ESTs
1267	24321	AI232340	o	Stromal cell-derived factor 1	Stromal cell-derived factor 1
1268	16172	AI232341	d		ESTs, Weakly similar to
					YQ42_CAEEL HYPOTHETICAL 40.0 KD
					PROTEIN C13B9.2 IN
					CHROMOSOME III [ C. elegans ]
1269	11411	AI232346	h		ESTs
1270	19287	AI232379	f	Platelet-derived growth	Platelet-derived growth factor receptor
				factor receptor alpha	alpha
1271	5601	AI232461	n, General		ESTs, Weakly similar to FMO1 RAT
					DIMETHYLANILINE
					MONOOXYGENASE [ R. norvegicus ]
1272	14051	AI232489	l, m		ESTs, Weakly similar to PIR1
					[ H. sapiens ]
1273	5572	AI232490	i, t		ESTs, Moderately similar to A27340
					complement C7 precursor [ H. sapiens ]
1274	11157	AI232494	cc		ESTs
1275	8709	AI232534	o		ESTs, Weakly similar to DnaJ
					homolog 2 [ R. norvegicus ]
1276	20350	AI232552	j, v, y		EST
1277	14069	AI232631	e		ESTs
1278	4440	AI232643	w		ESTs
1279	17695	AI232784	e		ESTs, Weakly similar to putative
					peroxisomal 2,4-dienoyl-CoA
					reductase [ R. norvegicus ]
1280	15796	AI232874	v		ESTs
1281	12467	AI232924	General		ESTs
1282	12873	AI232984	i		ESTs
1283	5355	AI233031	r		ESTs
1284	18794	AI233121	c		ESTs, Moderately similar to MHC
					class I [ M. musculus ]
1285	3823	AI233147	b, g,		ESTs, Weakly similar to nuclear RNA
			General		helicase [ R. norvegicus ]
1286	11967	AI233155	c, k,		ESTs
			General
1287	11561	AI233182	d		ESTs
1288	3471	AI233183	g		ESTs, Highly similar to PM1_HUMAN
					PROTEIN PM [ H. sapiens ]
1289	21948	AI233191	i		ESTs, Weakly similar to T15919
					hypothetical protein EEED8.9 -
					Caenorhabditis elegans [ C. elegans ]
1290	13598	AI233194	g, p, y		ESTs
1291	15552	AI233195	y		ESTs, Highly similar to Bodenin
					[ M. musculus ]
1292	17907	AI233224	bb		Rattus norvegicus epidermal growth
					factor receptor related protein (Errp)
					mRNA, complete cds
1293	14111	AI233269	cc		ESTs
1294	12894	AI233365	d		ESTs, Weakly similar to T24956
					hypothetical protein T16G1.10 -
					Caenorhabditis elegans [ C. elegans ]
1295	7161	AI233407	General		ESTs, Weakly similar to S44853
					K12H4.3 protein - Caenorhabditis
					elegans [ C. elegans ]
1296	15906	AI233425	q		ESTs
1297	14120	AI233433	d		ESTs
1298	14095	AI233468	a, d		ESTs
1299	3075	AI233494	u, aa		ESTs, Weakly similar to I38079 OXA1
					homolog [ H. sapiens ]
1300	6046	AI233530	General		ESTs
1301	18900	AI233570	General		PSD8_HUMAN 26S PROTEASOME
					REGULATORY SUBUNIT S14
					[ H. sapiens ]
1302	7888	AI233583	General	HHs: arginyl-tRNA	ESTs, Moderately similar to
				synthetase	SYR_HUMAN ARGINYL-TRNA
					SYNTHETASE [ H. sapiens ]
1303	16709	AI233602	General	Adenosin kinase	Adenosin kinase
1304	5163	AI233712	y		ESTs, Highly similar to
					P2CD_MOUSE PROTEIN
					PHOSPHATASE 2C DELTA
					ISOFORM (PP2C-DELTA) (P53-
					INDUCED PROTEIN PHOSPHATASE
					1) (PROTEIN PHOSPHATASE
					MAGNESIUM-DEPENDENT 1
					DELTA) [ M. musculus ]
1305	7243	AI233717	General		ESTs, Moderately similar to ERHUAH
					coatomer complex alpha chain
					homolog [ H. sapiens ]
1306	3816	AI233729	g		ESTs, Highly similar to
					PSD5_HUMAN 26S PROTEASOME
					SUBUNIT S5B [ H. sapiens ]
1307	13023	AI233740	d, h,		ESTs, Weakly similar to ALDR RAT
			General		ALDOSE REDUCTASE
					[ R. norvegicus ]
1308	14871	AI233743	g		ESTs
1309	7469	AI233767	cc		ESTs, Highly similar to Gene product
					with similarity to KIAA0154
					[ H. sapiens ]
1310	7804	AI233771	b		ESTs
1311	13563	AI233773	e		ESTs, Weakly similar to T24413
					hypothetical protein T04A11.2 -
					Caenorhabditis elegans [ C. elegans ]
1312	2154	AI233818	k, cc		ESTs
1313	16616	AI234079	h		ESTs
1314	13393	AI234100	a, d,	cysteine rich protein	cysteine rich protein
			General
1315	7071	AI234162	r		ESTs
1316	14677	AI234620	General		EST
1317	4443	AI234629	m		ESTs, Weakly similar to transcription
					factor C1 [ M. musculus ]
1318	22453	AI234678	b		ESTs
1319	23964	AI234748	t, General		ESTs
1320	19581	AI234753	f		EST
1321	22152	AI234822	o, General	DEXRAS1 (Dexras1)	DEXRAS1 (Dexras1)
1322	18942	AI234865	d		ESTs, Weakly similar to S12207
					hypothetical protein [ M. musculus ]
1323	22662	AI234939	aa	ATPase, H+ transporting,	ATPase, H+ transporting, lysosomal
				lysosomal (vacuolar proton	(vacuolar proton pump), subunit 1
				pump), subun
1324	3875	AI235047	o, General		ESTs, Highly similar to CB80_HUMAN
					80 KDA NUCLEAR CAP BINDING
					PROTEIN [ H. sapiens ]
1325	19479	AI235135	o		EST
1326	14906	AI235192	g		ESTs, Highly similar to ABF2_HUMAN
					ATP-BINDING CASSETTE, SUB-
					FAMILY F, MEMBER 2 (IRON
					INHIBITED ABC TRANSPORTER 2)
					[ H. sapiens ]
1327	14718	AI235210	e		ESTs
1328	15004	AI235224	b, General		Rattus norvegicus tissue inhibitor of
					metalloproteinase-1 (TIMP1), mRNA,
					complete cds
1329	6632	AI235277	v		ESTs
1330	14722	AI235284	x, z		ESTs, Weakly similar to single-pass
					transmembrane protein [ R. norvegicus ]
1331	1462	AI235585	u, General		Rat mRNA for preprocathepsin D (EC
					3.4.23.5)
1332	21061	AI235631	l, m		ESTs
1333	14665	AI235646	m	MAD homolog 4 ( Drosophila )	MAD homolog 4 ( Drosophila )
1334	19940	AI235689	General		ESTs, Moderately similar to pescadillo
					[ H. sapiens ]
1335	5698	AI235692	u		ESTs
1336	23745	AI235732	k		ESTs, Highly similar to NID2 MOUSE
					NIDOGEN-2 PRECURSOR
					[ M. musculus ]
1337	11164	AI235739	General		ESTs, Moderately similar to A56716
					aromatic ester hydrolase [ H. sapiens ]
1338	5212	AI235745	d		ESTs
1339	14768	AI235912	h		ESTs, Weakly similar to hypothetical
					protein [ H. sapiens ]
1340	14776	AI235950	m		ESTs
1341	3091	AI236027	n, General		ESTs
1342	14861	AI236045	r		ESTs
1343	14862	AI236048	e		EST
1344	16943	AI236097	p		ESTs, Highly similar to E25B protein
					[ M. musculus ]
1345	8336	AI236101	l		ESTs, Highly similar to JC7107
					development related unidentified 27K
					protein - mouse [ M. musculus ]
1346	23230	AI236146	v		ESTs
1347	22855	AI236150	e		ESTs, Highly similar to JC7301 Down
					syndrome critical region protein 5
					alpha [ H. sapiens ]
1348	14594	AI236152	i		ESTs
1349	18406	AI236168	r		ESTs
1350	15051	AI236332	General		ESTs, Highly similar to ATDA MOUSE
					DIAMINE ACETYLTRANSFERASE
					[ M. musculus ]
1351	19298	AI236338	bb		ESTs, Weakly similar to NHPX RAT
					NHP2/RS6 FAMILY PROTEIN
					YEL026W HOMOLOG [ R. norvegicus ]
1352	10667	AI236366	b	siah binding protein 1; FBP	siah binding protein 1; FBP interacting
				interacting repressor;	repressor; pyrimidine tract binding
				pyrimidine tr	splicing factor; Ro ribonucleoprotein-
					binding protein 1
1353	10774	AI236397	f		ESTs
1354	9407	AI236402	aa		ESTs
1355	26335	AI236460	General		Rattus norvegicus retinol
					dehydrogenase type II mRNA,
					complete cds
1356	17950	AI236590	t, General		ESTs
1357	18259	AI236601	h, v		ESTs
1358	11445	AI236613	j, y		ESTs
1359	17248	AI236635	o, aa		ESTs, Highly similar to SCF complex
					protein Skp1 [ M. musculus ]
1360	16859	AI236753	t, General		ESTs
1361	5208	AI236754	g		ESTs, Weakly similar to hT41
					[ H. sapiens ]
1362	24388	AI236772	e, General		ESTs
1363	15850	AI236795	n, v, w		ESTs, ESTs, Highly similar to HS9B
					RAT HEAT SHOCK PROTEIN HSP
					90-BETA [ R. norvegicus ]
1364	14800	AI236856	w		ESTs
1366	11404	AI237002	m	spermidine synthase	spermidine synthase
1367	18151	AI237212	o, General		ESTs, Highly similar to hepatitis B
					virus X interacting protein [ H. sapiens ]
1368	21553	AI237535	t, General	estrogen-responsive uterine	estrogen-responsive uterine transcript
				transcript
1369	11208	AI237586	z		ESTs, Moderately similar to INIB RAT
					INTERFERON-INDUCIBLE PROTEIN
					[ R. norvegicus ]
1370	21893	AI237713	i, k, aa		ESTs, Moderately similar to
					Y101_HUMAN HYPOTHETICAL
					PROTEIN KIAA0101 [ H. sapiens ]
1371	14842	AI237724	r		ESTs
1372	3467	AI237835	General		ESTs, Moderately similar to MXI1 RAT
					MAX INTERACTING PROTEIN 1
					[ R. norvegicus ]
1373	25840	AI638972	u
1374	17108	AI639017	n		ESTs, Highly similar to G9A
					[ M. musculus ]
1375	16676	AI639082	c, k, x	mini chromosome	mini chromosome maintenance
				maintenance deficient 6 ( S. cerevisiae )	deficient 6 ( S. cerevisiae )
1376	12400	AI639107	k		ESTs
1377	19952	AI639108	q, v		ESTs
1379	25907	AI639167	o, w		ESTs
1381	18533	AI639231	n		ESTs, Highly similar to T46480
					hypothetical protein
					DKFZp434L1850.1 [ H. sapiens ]
1382	18353	AI639233	t, aa	decorin	decorin
1384	15330	AI639285	General		ESTs
1385	20026	AI639354	g		EST
1386	25971	AI639365	r
1388	19152	AI639387	u, General		ESTs
1390	18338	AI639422	y		ESTs, Moderately similar to CAQC
					RAT CALSEQUESTRIN, CARDIAC
					MUSCLE ISOFORM PRECURSOR
					[ R. norvegicus ]
1392	20082	AI639488	i, m		EST, Highly similar to A42772 mdm2
					protein - rat [ R. norvegicus ]
1394	20056	AI639504	a, bb,		ESTs, Weakly similar to T13607
			General		hypothetical protein EG: 87B1.3 - fruit
					fly [ D. melanogaster ]
1395	4713	AI639518	q		ESTs, Highly similar to
					RPB8_HUMAN DNA-DIRECTED RNA
					POLYMERASES I, II, AND III 17.1 KD
					POLYPEPTIDE [ H. sapiens ]
1396	14332	AJ001044	bb	protein phosphatase 1,	protein phosphatase 1, regulatory
				regulatory (inhibitor) subunit 5	(inhibitor) subunit 5
1397	7602	AJ001929	k	reticulocalbin	reticulocalbin
1398	9867	AJ005424	u		Rattus norvegicus mRNA for
					BMK1/ERK5 protein, partial
1400	16351	AJ011811	General	claudin 7	claudin 7
1401	20116	AJ011969	l, General	growth differentiation factor	growth differentiation factor 15
				15
1402	17635	AJ223355	v, w		Rattus norvegicus mRNA for
					mitochondrial dicarboxylate carrier
1403	18686	D00729	q	dodecenoyl-Coenzyme A	Rat mRNA for delta3, delta2-enoyl-
				delta isomerase (3,2 trans-	CoA isomerase, dodecenoyl-
				enoyl-Coenyme A	Coenzyme A delta isomerase (3,2
					trans-enoyl-Coenyme A isomerase)
1404	5049	D10655	n, w	dihydrolipoamide	dihydrolipoamide acetyltransferase
				acetyltransferase
1405	25257	D13623	j
1405	15281	D13623	h		ESTs
1406	11434	D14014	cc		ESTs
1407	1613	D14076	x		Rat mRNA for testicular dynamin,
					complete cds
1408	1728	D16479	q	HHs: hydroxyacyl-Coenzyme	Rat mRNA for mitochondrial long-
				A dehydrogenase/3-ketoacyl-	chain 3-ketoacyl-CoA thiolase beta-
				Coenzyme A thiolase/enoyl-	subunit of mitochondrial trifunctional
				Coenzyme A hydralase	protein, complete dds
				(trifunctional protein), beta
				subunit
1409	3015	D16554	c, s, v, z		Rat mRNA for polyubiquitin (four
					repetitive ubiquitins in tandem),
					complete cds
1410	472	D26111	d, s, bb		R. norvegicus mRNA for chloride
					channel (putative) 2313bp
1412	16233	D29960	j, l		Rattus norvegicus mRNA for alphaB
					crystallin-related protein, complete cds
1413	9029	D30804	n		ESTs, Highly similar to PRC6 RAT
					PROTEASOME SUBUNIT RC6-1
					[ R. norvegicus ]
1414	1485	D38222	y, z		Rattus norvegicus tyrosine
					phosphatase-like protein IA-2a mRNA,
					partial cds
1415	9135	D45247	s	proteasome beta type	ESTs, Highly similar to PRCE RAT
				subunit 5	PROTEASOME EPSILON CHAIN
					PRECURSOR [ R. norvegicus ]
1416	16354	D50564	u	HHs: mercaptopyruvate	Rattus norvegicus mRNA for
				sulfurtransferase	mercaptopyruvate sulfurtransferase,
					complete cds
1417	1884	D50695	l, m, bb		Rattus norvegicus mRNA for
					proteasomal ATPase (Tat-binding
					protein7), complete cds
1418	21147	D63772	General	Solute carrier family 1 A1	Solute carrier family 1 A1 (brain
				(brain glutamate transporter)	glutamate transporter)
1419	826	D82928	f	HHs: CDP-diacylglycerol-	Rat mRNA for phosphatidylinositol
				inositol 3-	synthase, complete cds
				phosphatidyltransferase
				(phosphatidylinositol
				synthase)
1420	25306	D84485	u
1421	18867	D88250	t		Rattus norvegicus mRNA for serine
					protease, complete cds
1423	22543	H31117	r, v
			General
1424	12360	H31456	w		ESTs
1425	20514	H31489	h, j		ESTs
1426	11358	H31610	h		ESTs, Highly similar to mtprd
					[ M. musculus ]
1427	4360	H31813	bb,		ESTs, Moderately similar to T14781
			General		hypothetical protein
					DKFZp586B1621.1 [ H. sapiens ]
1428	9343	H32169	l		ESTs, Moderately similar to COF1
					RAT COFILIN, NON-MUSCLE
					ISOFORM [ R. norvegicus ]
1429	4386	H33093	h, w		EST
1430	4415	H33636	h		ESTs
1431	15374	H34186	l		ESTs, Highly similar to IF39_HUMAN
					EUKARYOTIC TRANSLATION
					INITIATION FACTOR 3 SUBUNIT 9
					[ H. sapiens ]
1432	17159	J00797	u, General	alpha-tubulin	alpha-tubulin
1433	16260	J01878	f		Rat brain-specific identifier sequence
					RNA, clone p1b224
1434	17284	J02827	bb	Branched chain alpha-	Branched chain alpha-ketoacid
				ketoacid dehydrogenase	dehydrogenase subunit E1 alpha
				subunit E1 alpha
1435	15017	J03752	n		Rat glutathione S-transferase mRNA,
					complete cds
1436	44	J03819	p, s	Thyroid hormone receptor,	Thyroid hormone receptor, beta (avian
				beta (avian erythroblastic	erythroblastic leukemia viral (v-erb-a)
				leukemia viral (v-erb-a)	oncogene homolog 2)
				oncogene homolog 2)
1437	21014	J03914	e, r,	Glutathione-S-transferase,	Glutathione-S-transferase, mu type 2
			General	mu type 2 (Yb2)	(Yb2)
1438	20429	J05035	f	Steroid-5-alpha-reductase,	Steroid-5-alpha-reductase, alpha
				alpha polypeptide 1 (3-oxo-5	polypeptide 1 (3-oxo-5 alpha-steroid
				alpha-steroid delta 4-	delta 4-dehydrogenase alpha 1)
				dehydrogenase alpha 1)
1439	1247	J05181	j, l, m, s, y, z	Glutamylcysteine gamma	Glutamylcysteine gamma synthetase
				synthetase light chain	light chain
1440	10464	J05510	n, u,	Inositol 1,4,5-triphosphate	Rat inositol-1,4,5-triphosphate
			General	receptor type 1	receptor mRNA, complete cds
1441	20149	K03243	q
1442	17758	K03249	q		Rat peroxisomal enoyl-CoA:
					hydrotase-3-hydroxyacyl-CoA
					bifunctional enzyme mRNA, complete
					cds
1443	381	L00124	w	Elastase 2, pancreatic	Elastase 2, pancreatic
1444	2048	L00382	k, x
1445	10500	L04619	s
1447	108	L14002	p		Rattus norvegicus clone 15 polymeric
					immunoglobulin receptor mRNA,
					3′UTR microsatellite repeats
1448	25366	L14003	t
1449	109	L14004	c, p		Rattus norvegicus clone 15 polymeric
					immunoglobulin receptor mRNA,
					3′UTR microsatellite repeats
1450	20414	L14323	General	Phospholipase C-beta1	Phospholipase C-beta1
1451	25369	L14937	y
1452	16119	L16532	k	2′,3′-Cyclic nucleotide 3′-	2′,3′-Cyclic nucleotide 3′-
				phosphodiesterase	phosphodiesterase
1453	25377	L25387	h
1453	12058	L25387	h		ESTs, Highly similar to A53047 6-
					phosphofructokinase [ R. norvegicus ]
1455	21146	L35558	General	Solute carrier family 1 A1	Solute carrier family 1 A1 (brain
				(brain glutamate transporter)	glutamate transporter)
1456	106	L37203	w		Rattus norvegicus guanylyl cyclase
					(GC-D) mRNA, complete cds
1458	13682	L38482	f, j, k, m, z		Rattus norvegicus serine protease
					gene, complete cds
1459	6405	L38615	p	Glutathione synthetase gene	Glutathione synthetase gene
1461	15189	M11794	n, v
1462	17086	M13011	j		Rat c-ras-H-1 gene, complete cds
1464	21053	M15481	o		Rat insulin-like growth factor-I mRNA,
					3′ end
1465	25405	M18330	j, l
1466	25415	M19648	a
1468	14967	M22366	w
1469	20481	M22631	bb	Propionyl Coenzyme A
				carboxylase, alpha
				polypeptide
1471	15048	M24542	q	HHs: ubiquinol-cytochrome c	Rat Rieske iron-sulfur protein mRNA,
				reductase, Rieske iron-sulfur	complete cds
				polypeptide 1
1472	20921	M29853	m		Rat cytochrome P-450 isozyme 5
					(P450 IVB2) mRNA, complete cds
1473	1224	M31931	u	Cytochrome P450, an	Cytochrome P450, an olfactory-
				olfactory-specific steroid	specific steroid hydroxylase
				hydroxylase
1474	15579	M33648	q		Rat mitochondrial 3-hydroxy-3-
					methylglutaryl-CoA synthase mRNA,
					complete cds
1474	15580	M33648	q		Rat mitochondrial 3-hydroxy-3-
					methylglutaryl-CoA synthase mRNA,
					complete cds
1475	17211	M34331	g, n, q, v		ESTs, Weakly similar to KRAB-zinc
					finger protein KZF-1 [ R. norvegicus ]
1476	20699	M35601	b, x, bb		Rat alpha-fibrinogen mRNA, 3′ end
1476	20700	M35601	b, t, bb		Rat alpha-fibrinogen mRNA, 3′ end
1477	9223	M36151	o		Rat mRNA for MHC class II antigen
					RT1.B-1 beta-chain, Rattus norvegicus
					MHC class II antigen RT1.B beta
					chain mRNA, partial cds
1479	1585	M57728	j, m, y		Rat general mitochondrial matrix
					processing protease (MPP) mRNA, 3′
					end
1480	24844	M58040	c	transferrin receptor	transferrin receptor
1481	25057	M58495	h
1482	457	M60666	d, General	Tropomyosin 1 (alpha)	Tropomyosin 1 (alpha)
1483	1223	M75281	f		Rat cystatin S (CysS) gene, complete
					cds
1484	5733	M81855	i, k, aa	P-glycoprotein/multidrug	P-glycoprotein/multidrug resistance 1
				resistance 1
1485	4198	M83143	m		Rat beta-galactoside-alpha 2,6-
					sialyltransferase mRNA
1485	4199	M83143	m		Rat beta-galactoside-alpha 2,6-
					sialyltransferase mRNA
1486	24651	M83678	k, x, z	RAB13	RAB13
1487	1430	M84648	General	Dopa decarboxylase	Dopa decarboxylase (aromatic L-
				(aromatic L-amino acid	amino acid decarboxylase)
				decarboxylase)
1488	25467	M93297	c	ornithine aminotransferase	ornithine aminotransferase
1489	729	M95762	a, y		Rattus norvegicus GABA transporter
					GAT-2 mRNA, complete cds
1490	23698	NM_012489	q	Rattus norvegicus Acetyl-	Acetyl-CoA acyltransferase, 3-oxo
				CoA acyltransferase, 3-oxo	acyl-CoA thiolase A, peroxisomal
				acyl-CoA thiolase A,
				peroxisomal (Acaa), mRNA.
				Length = 1619
1490	23699	NM_012489	q	Rattus norvegicus Acetyl-	Acetyl-CoA acyltransferase, 3-oxo
				CoA acyltransferase, 3-oxo	acyl-CoA thiolase A, peroxisomal
				acyl-CoA thiolase A,
				peroxisomal (Acaa), mRNA.
				Length = 1619
1491	7062	NM_012495	q	Rattus norvegicus Aldolase	Aldolase A, fructose-bisphosphate
				A, fructose-bisphosphate
				(Aldoa), mRNA. Length = 1442
1492	15511	NM_012498	u	Rattus norvegicus Aldehyde	Aldehyde reductase 1 (low Km aldose
				reductase 1 (low Km aldose	reductase) (5.8 kb Pstl fragment,
				reductase) (5.8 kb Pstl	probably the functional gene)
				fragment, probably the
				functional gene) (Akr1b1),
				mRNA. Length = 1339
1494	7427	NM_012515	General	Rattus norvegicus	Benzodiazepin receptor (peripheral)
				Benzodiazepin receptor
				(peripheral) (Bzrp), mRNA.
				Length = 781
1495	24433	NM_012527	i	Rattus norvegicus	Cholinergic receptor, muscarinic 3
				Cholinergic receptor,
				muscarinic 3 (Chrm3),
				mRNA. Length = 3578
1496	4467	NM_012529	d	Rattus norvegicus Creatine	Creatine kinase, brain
				kinase, brain (Ckb), mRNA.
				Length = 1146
1497	16520	NM_012532	General	Rattus norvegicus	Ceruloplasmin (ferroxidase)
				Ceruloplasmin (ferroxidase)
				(Cp), mRNA. Length = 3700
1498	225	NM_012544	x, z	Rattus norvegicus	Dipeptidyl carboxypeptidase 1
				Angiotensin I-converting	(Angiotensin I-converting enzyme)
				enzyme (Dipeptidyl
				carboxypeptidase 1) (Ace),
				mRNA. Length = 4142
1499	1431	NM_012545	General	Rattus norvegicus Dopa	Dopa decarboxylase (aromatic L-
				decarboxylase (aromatic L-	amino acid decarboxylase)
				amino acid decarboxylase)
				(Ddc), mRNA. Length = 1954
1500	23868	NM_012551	l, m, v,	Rattus norvegicus Early	Early growth response 1
			General	growth response 1 (Egr1),
				mRNA. Length = 3112
1500	23872	NM_012551	l, v, cc,	Rattus norvegicus Early	Early growth response 1
			General	growth response 1 (Egr1),
				mRNA. Length = 3112
1500	23869	NM_012551	v, General	Rattus norvegicus Early	Early growth response 1
				growth response 1 (Egr1),
				mRNA. Length = 3112
1501	19407	NM_012554	z	Rattus norvegicus Enolase	Enolase 1, alpha
				1, alpha (Eno1), mRNA.
				Length = 1725
1501	19408	NM_012554	n, s, y, z	Rattus norvegicus Enolase	Enolase 1, alpha
				1, alpha (Eno1), mRNA.
				Length = 1725
1502	21836	NM_012555	k	Rattus norvegicus Ets avian	Ets avian erythroblastosis virus E2
				erythroblastosis virus E2	oncogene homolog 1 (tumor
				oncogene homolog 1 (tumor	progression locus 1)
				progression locus 1) (Ets1),
				mRNA. Length = 4991
1503	16895	NM_012558	g, s	Rattus norvegicus Fructose-	Fructose-1,6-biphosphatase
				1,6-biphosphatase (Fbp1),
				mRNA. Length = 1357
1504	25317	NM_012559	bb	Rattus norvegicus
				Fibrinogen, gamma
				polypeptide (Fgg), mRNA.
				Length = 1358
1504	6477	NM_012559	b, bb	Rattus norvegicus	Fibrinogen, gamma polypeptide
				Fibrinogen, gamma
				polypeptide (Fgg), mRNA.
				Length = 1358
1504	6478	NM_012559	bb	Rattus norvegicus	Fibrinogen, gamma polypeptide
				Fibrinogen, gamma
				polypeptide (Fgg), mRNA.
				Length = 1358
1505	11731	NM_012561	k	Rattus norvegicus Follistatin	Follistatin
				(Fst), mRNA. Length = 1035
1507	4254	NM_012564	a	Rattus norvegicus Group-	Group-specific component (vitamin D-
				specific component (vitamin	binding protein)
				D-binding protein) (Gc),
				mRNA. Length = 1676
1508	16026	NM_012578	r	Rattus norvegicus Histone	Histone H1-0
				H1-0 (H1f0), mRNA. Length = 1779
1508	16024	NM_012578	r	Rattus norvegicus Histone	Histone H1-0
				H1-0 (H1f0), mRNA. Length = 1779
1508	16025	NM_012578	r	Rattus norvegicus Histone	Histone H1-0
				H1-0 (H1f0), mRNA. Length = 1779
1509	16080	NM_012580	g, m	Rattus norvegicus Heme	Heme oxygenase
				oxygenase (Hmox1), mRNA.
				Length = 870
1510	15098	NM_012588	bb	Rattus norvegicus insulin-	Insulin-like growth factor-binding
				like growth factor-binding	protein (IGF-BP3)
				protein (IGF-BP3) (Igfbp3),
				mRNA. Length = 2352
1511	4450	NM_012592	bb	Rattus norvegicus Isovaleryl	Isovaleryl Coenzyme A
				Coenzyme A dehydrogenase	dehydrogenase
				(Ivd), mRNA. Length = 2104
1511	4451	NM_012592	i, bb	Rattus norvegicus Isovaleryl	Isovaleryl Coenzyme A
				Coenzyme A dehydrogenase	dehydrogenase
				(Ivd), mRNA. Length = 2104
1511	4452	NM_012592	bb	Rattus norvegicus Isovaleryl	Isovaleryl Coenzyme A
				Coenzyme A dehydrogenase	dehydrogenase
				(Ivd), mRNA. Length = 2104
1512	17198	NM_012593	a, x	Rattus norvegicus Kallikrein	Kallikrein 1, renal/pancreas/salivary
				1, renal/pancreas/salivary
				(Klk1), mRNA. Length = 786
1512	17197	NM_012593	x	Rattus norvegicus Kallikrein	Kallikrein 1, renal/pancreas/salivary
				1, renal/pancreas/salivary
				(Klk1), mRNA. Length = 786
1513	18749	NM_012600	a, h	Rattus norvegicus Malic	Malic enzyme 1, soluble
				enzyme 1, soluble (Me1),
				mRNA. Length = 1761
1514	2628	NM_012603	General	Rattus norvegicus Avian	Avian myelocytomatosis viral (v-myc)
				myelocytomatosis viral (v-	oncogene homolog
				myc) oncogene homolog
				(Myc), mRNA. Length = 2168
1514	2629	NM_012603	x, General	Rattus norvegicus Avian	Avian myelocytomatosis viral (v-myc)
				myelocytomatosis viral (v-	oncogene homolog
				myc) oncogene homolog
				(Myc), mRNA. Length = 2168
1515	16849	NM_012608	n, o, q	Rattus norvegicus	Membrane metallo-endopeptidase
				Membrane metallo-	(neutral
				endopeptidase (neutral	endopeptidase/enkephalinase)
				endopeptidase/enkephalinase)
				(Mme), mRNA. Length = 3243
1517	15540	NM_012620	General	Rattus norvegicus serine (or	Plasminogen activator inhibitor
				cysteine) proteinase
				inhibitor. clade E (nexin,
				plasminogen activator
				inhibitor type 1), member 1
				(Serpine1), mRNA. Length = 3053
1518	24568	NM_012630	General	Rattus norvegicus Prolactin	Prolactin receptor
				receptor (Prlr), mRNA.
				Length = 1635
1518	24566	NM_012630	General	Rattus norvegicus Prolactin	Prolactin receptor
				receptor (Prlr), mRNA.
				Length = 1635
1519	18553	NM_012631	k	Rattus norvegicus Prion	Prion protein, structural
				protein, structural (Pmp),
				mRNA. Length = 765
1520	1844	NM_012637	General	Rattus norvegicus protein	ESTs, Protein-tyrosine phosphatase
				tyrosine phosphatase, non-
				receptor type 1 (Ptpn1),
				mRNA. Length = 4127
1521	24668	NM_012642	f	Rattus norvegicus Renin	Renin
				(Ren), mRNA. Length = 1059
1522	18632	NM_012645	a	Rattus norvegicus RT1 class	RT1 class lb gene
				lb gene (RT1Aw2), mRNA.
				Length = 1540
1523	25435	NM_012647	g	Rattus norvegicus Sodium
				channel. voltage-gated, type
				II, alpha polypeptide
				(Scn2a1), mRNA. Length = 8553
1524	9423	NM_012649	b, cc	Rattus norvegicus	Ryudocan/syndecan 4
				Ryudocan/syndecan 4
				(Sdc4), mRNA. Length = 2462
1525	24496	NM_012654	n	Rattus norvegicus Solute	Solute carrier family 9
				carrier family 9	(sodium/hydrogen exchanger 3),
				(sodium/hydrogen exchanger	antiporter 3, Na+/H+ (amiloride
				3), antiporter 3, Na+/H+	insensitive)
				(amiloride insensitive)
				(Slc9a3), mRNA. Length = 5153
1526	7101	NM_012679	x, bb,	Rattus norvegicus Clusterin	Testostrone-repressed prostate
			General	(Clu), mRNA. Length = 1638	message 2
1527	24707	NM_012693	i	Rattus norvegicus	Cytochrome P450 IIA2
				Cytochrome P450 IIA2
				(Cyp2a2), mRNA. Length = 2259
1528	1850	NM_012696	t	Rattus norvegicus T-	T-kininogen
				kininogen, see also D11Elh1
				and D11Mit8 (Kng), mRNA.
				Length = 1417
1528	1854	NM_012696	t	Rattus norvegicus T-	K-kininogen, differential splicing leads
				kininogen, see also D11Elh1	to HMW Kngk, T-kininogen
				and D11Mit8 (Kng), mRNA.
				Length = 1417
1529	1603	NM_012697	General	Rattus norvegicus Organic	Organic cation transporter
				cation transporter (Slc22a1),
				mRNA. Length = 1882
1530	1372	NM_012734	u	Rattus norvegicus	Hexokinase 1
				Hexokinase 1 (Hk1), mRNA.
				Length = 3653
1531	1478	NM_012744	bb,	Rattus norvegicus Pyruvate	Pyruvate carboxylase
			General	carboxylase (Pc), mRNA.
				Length = 3945
1532	343	NM_012747	h, t	Rattus norvegicus Signal	Signal transducer and activator of
				transducer and activator of	transcription 3
				transcription 3 (Stat3),
				mRNA. Length = 2924
1533	8829	NM_012749	General	Rattus norvegicus Nucleolin	Nucleolin
				(Ncl), mRNA. Length = 2142
1534	20828	NM_012752	General	Rattus norvegicus CD24	CD24 antigen
				antigen (Cd24), mRNA.
				Length = 1703
1534	20829	NM_012752	i, General	Rattus norvegicus CD24	CD24 antigen
				antigen (Cd24), mRNA.
				Length = 1703
1534	20830	NM_012752	i, General	Rattus norvegicus CD24	CD24 antigen
				antigen (Cd24), mRNA.
				Length = 1703
1535	15174	NM_012756	b	Rattus norvegicus Insulin-	Insulin-like growth factor 2 receptor
				like growth factor 2 receptor
				(Igf2r), mRNA. Length = 8810
1536	21685	NM_012760	j, m, n	Rattus norvegicus Lost on	Lost on transformation 1
				transformation 1 (Lot1),
				mRNA. Length = 5028
1537	18068	NM_012762	t	Rattus norvegicus Interleukin	Interleukin 1beta converting enzyme
				1beta converting enzyme
				(Casp1), mRNA. Length = 1209
1538	1246	NM_012770	a, General	Rattus norvegicus Guanylate	Guanylate cyclase, soluble, beta 2
				cyclase, soluble, beta 2	(GTP pyrophosphate - lyase)
				(GTP pyrophosphate - lyase)
				(Gucy1b2), mRNA. Length = 2335
1539	1348	NM_012776	f	Rattus norvegicus	G-protein-linked receptor kinase (beta
				adrenergic receptor kinase,	adrenergic receptor kinase 1)
				beta 1 (Adrbk1), mRNA.
				Length = 2683
1540	18135	NM_012791	w	Rattus norvegicus dual-	Dual Specificity Yak1-related
				specificity tyrosine-(Y)-	kinase, ESTs
				phosphorylation regulated
				kinase 1a (Dyrk1a), mRNA.
				Length = 2840
1541	16947	NM_012793	p, bb	Rattus norvegicus	Guanidinoacetate methyltransferase
				Guanidinoacetate
				methyltransferase (Gamt),
				mRNA. Length = 924
1542	960	NM_012796	u	Rattus norvegicus	glutathione S-transferase, theta 2
				glutathione S-transferase,
				theta 2 (Gstt2), mRNA.
				Length = 1258
1543	260	NM_012798	f, u	Rattus norvegicus MAL	MAL protein gene
				protein gene (Mal), mRNA.
				Length = 2268
1544	556	NM_012803	d	Rattus norvegicus Protein C	Protein C
				(Proc), mRNA. Length = 1543
1545	21729	NM_012804	q	Rattus norvegicus ATP-	ATP-binding cassette, sub-family D
				binding cassette, sub-family	(ALD), member 3
				D (ALD), member 3 (Abcd3),
				mRNA. Length = 3324
1546	15032	NM_012816	General	Rattus norvegicus alpha-	Methylacyl-CoA racemase alpha
				methylacyl-CoA racemase
				(Amacr), mRNA. Length = 1504
1547	24895	NM_012817	General	Rattus norvegicus Insulin-	Insulin-like growth factor-binding
				like growth factor-binding	protein 5
				protein 5 (lgfbp5), mRNA.
				Length = 1630
1548	18109	NM_012823	u, General	Rattus norvegicus Annexin	ESTs, Weakly similar to LURT3
				A3 (Anx3), mRNA. Length = 1454	annexin III - rat [ R. norvegicus ]
1549	373	NM_012833	h, l, q,	Rattus norvegicus ATP-	Canalicular multispecific organic anion
			General	binding cassette, sub-family	transporter
				C (CFTR/MRP), member 2
				(Abcc2), mRNA. Length = 4918
1550	2855	NM_012838	e	Rattus norvegicus Cystatin	Cystatin beta
				beta (Cstb), mRNA. Length = 590
1551	11136	NM_012839	s	Rattus norvegicus	Cytochrome C, expressed in somatic
				Cytochrome C, expressed in	tissues
				somatic tissues (Cycs),
				mRNA. Length = 318
1552	20885	NM_012842	a	Rattus norvegicus Epidermal	Epidermal growth factor
				growth factor (Egf), mRNA.
				Length = 4801
1552	20884	NM_012842	a, bb	Rattus norvegicus Epidermal	Epidermal growth factor
				growth factor (Egf), mRNA.
				Length = 4801
1553	18770	NM_012857	e	Rattus norvegicus	Lysosomal associated membrane
				Lysosomal associated	protein 1 (120 kDa)
				membrane protein 1 (120 kDa)
				(Lamp1), mRNA.
				Length = 2006
1554	20674	NM_012861	i	Rattus norvegicus O6-	ESTs, Weakly similar to S21348
				methylguanine-DNA	probable pol polyprotein-related
				methyltranferase (Mgmt),	protein 4 - rat [ R. norvegicus ], O6-
				mRNA. Length = 812	methylguanine-DNA methyltranferase
1555	13151	NM_012862	a, r,	Rattus norvegicus Matrix Gla	Matrix Gla protein
			General	protein (Mgp), mRNA.
				Length = 521
1556	24617	NM_012870	General	Rattus norvegicus tumor	Osteoprotegerin
				necrosis factor receptor
				superfamily, member 11b
				(osteoprotegerin)
				(Tnfrsf11b), mRNA. Length = 2432
1557	20945	NM_012875	a, v	Ribosomal protein L39	Ribosomal protein L39
				(Rpl39), mRNA. Length = 324
1558	15872	NM_012879	o, r	Rattus norvegicus Solute	Solute carrier family 2 A2 (gkucose
				carrier family 2 A2 (gkucose	transporter, type 2)
				transporter, type 2) (Slc2a2),
				mRNA. Length = 2573
1559	495	NM_012880	z	Rattus norvegicus	Superoxide dimutase 3
				Superoxide dismutase 3
				(Sod3), mRNA. Length = 1729
1559	494	NM_012880	c	Rattus norvegicus	Superoxide dimutase 3
				Superoxide dismutase 3
				(Sod3), mRNA. Length = 1729
1560	23651	NM_012881	d, u,	Rattus norvegicus	Sialoprotein (osteopontin)
			General	Sialoprotein (osteopontin)
				(Spp1), mRNA. Length = 1457
1562	19477	NM_012891	q	Rattus norvegicus Acyl-Coa	EST, Moderately similar to ACDV RAT
				dehydrogenase, Very long	ACYL-COA DEHYDROGENASE,
				chain (Acadvt), mRNA.	VERY-LONG-CHAIN SPECIFIC,
				Length = 2117	MITOCHONDRIAL PRECURSOR
					[ R. norvegicus ]
1563	18564	NM_012899	v, General	Rattus norvegicus	Delta - aminolevulinic acid
				aminolevulinate, delta-,	dehydratase
				dehydratase (Alad), mRNA.
				Length = 1116
1564	7197	NM_012904	f, r, cc, General	Rattus norvegicus Annexin 1	Annexin 1 (p35) (Lipocortin 1)
				(p35) (Lipocortin 1) (Anxa1),
				mRNA. Length = 1402
1564	7196	NM_012904	v, cc,	Rattus norvegicus Annexin 1	Annexin 1 (p35) (Lipocortin 1)
			General	(p35) (Lipocortin 1) (Anxa1),
				mRNA. Length = 1402
1565	20202	NM_012909	b, r	Rattus norvegicus Aquaporin	Aquaporin 2
				2 (Aqp2), mRNA. Length = 939
1566	16581	NM_012911	c, j	Rattus norvegicus Arrestin,	Arrestin, beta 2
				beta 2 (Arrb2), mRNA.
				Length = 1758
1566	16582	NM_012911	c	Rattus norvegicus Arrestin,	Arrestin, beta 2
				beta 2 (Arrb2), mRNA.
				Length = 1758
1567	24431	NM_012912	General	Rattus norvegicus Activating	Activating transcription factor 3
				transcription factor 3 (Atf3),
				mRNA. Length = 1893
1568	18118	NM_012913	p	Rattus norvegicus ATPase,	ATPase, Na+K+ transporting, beta
				Na+K+ transporting, beta	polypeptide 3
				polypeptide 3 (Atp1b3),
				mRNA. Length = 1818
1569	6108	NM_012915	n	Rattus norvegicus ATPase	ATPase inhibitor (rat mitochondrial IF1
				inhibitor (rat mitochondrial	protein)
				IF1 protein) (Atpi), mRNA.
				Length = 833
1570	20757	NM_012923	c, i, aa	Rattus norvegicus Cyclin G1	Cyclin G1
				(Ccng1), mRNA. Length = 3169
1570	20755	NM_012923	i	Rattus norvegicus Cyclin G1	Cyclin G1
				(Ccng1), mRNA. Length = 3169
1571	2830	NM_012925	f	Rattus norvegicus CD59	CD59 antigen
				antigen (Cd59), mRNA.
				Length = 1523
1571	2831	NM_012925	f	Rattus norvegicus CD59	CD59 antigen
				antigen (Cd59), mRNA.
				Length = 1523
1572	1977	NM_012930	q	Rattus norvegicus Carnitine	Carnitine palmitoyltransferase 2
				palmitoyltransferase 2
				(Cpt2), mRNA. Length = 2296
1573	18694	NM_012931	j, l, m, z	Rattus norvegicus v-crk-	v-crk-associated tyrosine kinase
				associated tyrosine kinase	substrate
				substrate (Crkas), mRNA.
				Length = 3335
1574	13723	NM_012935	n	Rattus norvegicus Crystallin,	Crystallin, alpha polypeptide 2, ESTs
				alpha polypeptide 2 (Cryab),
				mRNA. Length = 528
1575	9109	NM_012939	j, y, z	Rattus norvegicus Cathepsin	Cathepsin H
				H (Ctsh), mRNA. Length = 1362
1575	19398	NM_012939	aa	Rattus norvegicus Cathepsin	EST
				H (Ctsh), mRNA. Length = 1362
1576	223	NM_012945	b, cc	Rattus norvegicus Diphtheria	Diphtheria toxin receptor (heparin
				toxin receptor(heparin	binding epidermal growth factor - like
				binding epidermal growth	growth factor)
				factor - like growth factor)
				(Dtr), mRNA. Length = 1550
1577	15058	NM_012950	cc	Rattus norvegicus Thrombin	Thrombin receptor
				receptor (F2r), mRNA.
				Length = 3418
1579	19111	NM_012963	g	Rattus norvegicus High	High mobility group 1
				mobility group 1 (Hmg1),
				mRNA. Length = 1225
1580	19374	NM_012964	x	Rattus norvegicus	Hyaluronan mediated motility receptor
				Hyaluronan mediated motility	(RHAMM)
				receptor (RHAMM) (Hmmr),
				mRNA. Length = 2049
1581	2554	NM_012967	t	Rattus norvegicus	Intercellular adhesion molecule 1
				Intercellular adhesion
				molecule 1 (Icam1), mRNA.
				Length = 2602
1581	2555	NM_012967	t, cc,	Rattus norvegicus	Intercellular adhesion molecule 1
			General	Intercellular adhesion
				molecule 1 (Icam1), mRNA.
				Length = 2602
1582	24528	NM_012973	c	Rattus norvegicus Potassium	Potassium (K+) channel protein,
				(K+) channel protein, slowly	slowly activating (Isk)
				activating (Isk) (Kcne1),
				mRNA. Length = 585
1583	956	NM_012976	c	Rattus norvegicus Lectin,	Lectin, galactose binding, soluble 9
				galactose binding, soluble 5	(Galectin-9)
				(Galectin-5) (Lgals5), mRNA.
				Length = 872
1584	16417	NM_012991	g	Rattus norvegicus	Nuclear pore associated protein
				Nucleoprotein 50 kD (Nup50),
				mRNA. Length = 3027
1585	17393	NM_012992	d	Rattus norvegicus	Nucleoplasmin-related protein
				Nucleoplasmin-related	(Nuclear protein B23
				protein (Nuclear protein B23
				(Npm1), mRNA. Length = 1232
1586	23544	NM_013013	s	Rattus norvegicus	Prosaposin (sulfated glycoprotein,
				Prosaposin (sulfated	sphingolipid hydrolase activator)
				glycoprotein, sphingolipid
				hydrolase activator) (Psap),
				mRNA. Length = 2175
1587	1588	NM_013026	k	Rattus norvegicus Syndecan	Syndecan 1
				1 (Sdc1), mRNA. Length = 2410
1588	17894	NM_013027	m	Rattus norvegic