Gene Set: WENG_POR_DOSAGE

Standard name WENG_POR_DOSAGE
Systematic name M1634
Brief description Genes up-regulated in liver from mice with liver specific knockout of POR [GeneID=5447] vs mice with reduced expression of POR in all tissues.
Full description or abstract NADPH-cytochrome P450 reductase (CPR) is an essential component for the function of many enzymes, including microsomal cytochrome P450 (P450) monooxygenases and heme oxygenases. In liver-Cpr-null (with liver-specific Cpr deletion) and Cpr-low (with reduced CPR expression in all organs examined) mouse models, a reduced serum cholesterol level and an induction of hepatic P450s were observed, whereas hepatomegaly and fatty liver were only observed in the liver-Cpr-null model. Our goal was to identify hepatic gene expression changes related to these phenotypes. Cpr-lox mice (with a floxed Cpr gene and normal CPR expression) were used as the control. Through microarray analysis, we identified many genes that were differentially expressed among the three groups of mice. We also recognized the 12 gene ontology terms that contained the most significantly changed gene expression in at least one of the two mouse models. We further uncovered potential mechanisms, such as an increased activation of constitutive androstane receptor and a decreased activation of peroxisomal proliferator-activated receptor-alpha by precursors of cholesterol biosynthesis, that underlie common changes (e.g. induction of multiple P450s and suppression of genes for fatty acid metabolism) in response to CPR loss in the two mouse models. Additionally, we observed model-specific gene expression changes, such as the induction of a fatty-acid translocase (Cd36 antigen) and the suppression of carnitine O-palmitoyltransferase 1 (Cpt1a) and acyl-CoA synthetase long chain family member 1 (Acsl1), that are potentially responsible for the severe hepatic lipidosis and an altered fatty acid profile observed in liver-Cpr-null mice.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16006652   Authors: Weng Y,DiRusso CC,Reilly AA,Black PN,Ding X
Exact source Table 1: Liver-Cpr-null/Cpr-low >= 2
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Organism Mus musculus
Contributed by John Newman (University of Washington)
Source platform MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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