Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA192623 | ENA |
REPOSITORIES: ENA
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Project description:Mdr1a-, Bcrp-, and Mrp2-knockout rats are a more practical species for ADME studies than murine models and previously demonstrated expected alterations in pharmacokinetics of various probe substrates. At present, gene expression and pathology changes were systematically studied in small intestine, liver, kidney, and brain tissue from male SAGE Mdr1a-, Bcrp-, and Mrp2-knockout rats versus wild-type Sprague Dawley controls. Gene expression data supported the relevant knockout genotype. As expected, Mrp2-knockout rats were hyperbilirubinemic and exhibited upregulation of hepatic Mrp3. Overall, few alterations were observed within 137 ADME-relevant genes. The two most consequential changes were upregulation of intestinal carboxylesterase in Mdr1a-knockouts and catechol-O-methyltransferase in all tissues of Bcrp-knockout rats. Previously reported upregulation of hepatic Mdr1b P-glycoprotein in proprietary Wistar Mdr1a-knockout rats was not observed in the SAGE counterpart investigated herein. Relative liver and kidney weights were 22-53% higher in all three knockouts, with microscopic increases in hepatocyte size in Mdr1a- and Mrp2-knockout rats, and glomerular size in Bcrp- and Mrp2-knockouts. Increased relative weight of clearing organs is quantitatively consistent with reported increases in clearance of drugs that are not substrates of the knocked-out transporter. Overall, SAGE knockout rats demonstrated modest compensatory changes, which do not preclude their general application to study transporter-mediated pharmacokinetics. However until future studies elucidate the magnitude of functional change, caution is warranted in rare instances of extensive metabolism by catechol-O-methyltransferase in Bcrp-knockouts and intestinal carboxylesterase in Mdr1a-knockout rats, specifically for molecules with free catechol groups and esters subject to gut wall hydrolysis. 3 groups of knockout animals compared to wild-type male Sprague Dawley control rats. 4 animals per group. Assayed the following tissues: brain, duodenum, ileum, jejunum, kidney (cortex-anterior pole), kidney (medulla), liver. Hybridized to Affymetrix Rat Genome 230 v2 [Rat230_2] arrays.
2013-04-08 | E-GEOD-44962 | biostudies-arrayexpress
Project description:Mdr1a-, Bcrp-, and Mrp2-knockout rats are a more practical species for ADME studies than murine models and previously demonstrated expected alterations in pharmacokinetics of various probe substrates. At present, gene expression and pathology changes were systematically studied in small intestine, liver, kidney, and brain tissue from male SAGE Mdr1a-, Bcrp-, and Mrp2-knockout rats versus wild-type Sprague Dawley controls. Gene expression data supported the relevant knockout genotype. As expected, Mrp2-knockout rats were hyperbilirubinemic and exhibited upregulation of hepatic Mrp3. Overall, few alterations were observed within 137 ADME-relevant genes. The two most consequential changes were upregulation of intestinal carboxylesterase in Mdr1a-knockouts and catechol-O-methyltransferase in all tissues of Bcrp-knockout rats. Previously reported upregulation of hepatic Mdr1b P-glycoprotein in proprietary Wistar Mdr1a-knockout rats was not observed in the SAGE counterpart investigated herein. Relative liver and kidney weights were 22-53% higher in all three knockouts, with microscopic increases in hepatocyte size in Mdr1a- and Mrp2-knockout rats, and glomerular size in Bcrp- and Mrp2-knockouts. Increased relative weight of clearing organs is quantitatively consistent with reported increases in clearance of drugs that are not substrates of the knocked-out transporter. Overall, SAGE knockout rats demonstrated modest compensatory changes, which do not preclude their general application to study transporter-mediated pharmacokinetics. However until future studies elucidate the magnitude of functional change, caution is warranted in rare instances of extensive metabolism by catechol-O-methyltransferase in Bcrp-knockouts and intestinal carboxylesterase in Mdr1a-knockout rats, specifically for molecules with free catechol groups and esters subject to gut wall hydrolysis.
2013-04-08 | GSE44962 | GEO
Project description:SAGE profile of rat hippocampus mRNA from Wistar rats
2010-12-01 | GSE25750 | GEO
Project description:SAGE profile of the rat superior olivary complex (SOC). Rats were 60 days old (P60). Keywords: other
2004-12-13 | GSE2063 | GEO
Project description:Thirty-two SD rats (male, 150 grams, 50days) were randomly divided into four groups: normal control group, asthma group, acupuncture-treated asthma group and acupuncture-treated normal group. The rat lungs were removed immediately after the rats were died. The rat lungs were conserved in liquid nitrogen. SAGE analyses were dependent on the classic protocol (Velculescu VE, et al, Serial Analysis of Gene Expression Detailed Protocol, version 1.0e, 2000) available at the SAGENET website. Keyword = Rat Keyword = Lung Keyword = Asthma Keyword = SAGE Keyword = Acupuncture Keywords: disease state analysis
2005-04-09 | GSE2475 | GEO
Project description:Orally administered drugs are absorbed and metabolized in the intestine. In order to accurately predict pharmacokinetics in the intestine, it is essential to understand the intestinal expression profiles of genes related to drug absorption, distribution, metabolism, and excretion (ADME). However, in many previous studies, gene expression analysis in the intestine has been carried out using specimens from cancer patients. In this study, in order to obtain a more accurate gene expression profile, biopsy samples were collected from 14 patients under endoscopic observation and RNA-seq analysis was performed. Gene expression analysis of drug metabolizing enzymes (CYPs), non-CYP enzymes, nuclear receptors, drug conjugating enzymes (UGTs and SULTs), and apical and basolateral drug transporters was performed in biopsy samples from the duodenum, ileum, colon, and rectum. The proportions of the CYPs expressed in the ileum were 25% (CYP3A4), 19% (CYP2C18), and 14% (CYP3A5). CYP3A4 and CYP2C19 were highly expressed in the duodenum and ileum, but not in the colon and rectum. In the ileum, apical transporters such as P-gp, PEPT1, BCRP, MRP2, and ASBT were strongly expressed, and the expression levels of P-gp and ASBT in the ileum were higher than those in other regions. In the ileum, basolateral transporters such as OSTα, OSTβ, and MRP3 were strongly expressed. Furthermore, we identified specific markers for the duodenum, ileum, colon, and rectum by conducting comprehensive gene expression analysis. We succeeded in obtaining gene expression profiles of drug ADME-related genes in vivo human intestinal epithelial cells. We expect that this information would be useful for accurate prediction of the pharmacokinetics of oral drugs.
2021-04-30 | GSE156453 | GEO
Project description:SAGE analysis of genes expressed in rat brain microvessels. Keywords: Novel gene identification Microvessels were pooled from 50 rats, a single SAGE library was constructed from the microvessel RNA
2005-12-02 | E-GEOD-3696 | biostudies-arrayexpress
Project description:Human Ulcerative colitis (UC) is characterized by chronic colonic inflammation and has been associated with an increased risk of colorectal carcinoma. Gene and protein expression profiles of ABCB1/MDR1 have been shown to be dysregulated in UC and sporadic colorectal cancer. We demonstrated that in a murine model of colitis-associated tumorigenesis, MDR1A KO mice showed reduced tumor load when compared to wildtype (WT) mice. The aim of this study was to identify gene alterations in colitis-associated tumors in the context of MDR1A deficiency. We used microarrays to assess gene expression profiles of colitis-associated colonic tumors from WT or MDR1A KO mice.
2017-06-17 | GSE94960 | GEO
Project description:Aging is associated with a decline in hippocampal mediated learning and memory, a process wich can be ameliorated by dietary (caloric) restriction. We used Affymetrix gene expression analysis to monitor changes in three regions of the hippocampus (CA1, CA3, DG) of middle aged (18 months) and old (28 month) rats that were exposed to dietary restriction. Old rats were determined to be good performers (GP) or poor performers (PP) in behavioral tests to assess thier hippocampal function.
2010-05-25 | GSE21681 | GEO
Project description:The study aimed to find out quantitative changes at the protein level in the total membrane fraction enriched in synaptosomes and mitochondria upon the absence of the dopamine transporter in rat brain. Therefore, the brain of male rats (Wister Han) DAT-wildtype and DAT-knockout animals, were dissected and the striatum was used for the enrichment of the synaptic and mitochondrial membrane fraction. The proteins of the total membrane fraction were further tryptically digested and analysed via label-free LC-MSMS.
2022-05-19 | PXD028157 | Pride