STANDARD_NAME	WENG_POR_TARGETS_GLOBAL_DN
SYSTEMATIC_NAME	M1615
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WENG_POR_TARGETS_GLOBAL_DN
NAMESPACE	Mouse_RefSeq
DESCRIPTION_BRIEF	Genes down-regulated in liver from transgenic mice with reduced expression of POR [GeneID=5447] in all tissues.
DESCRIPTION_FULL	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.
PMID	16006652
GEOID	GSE2362
AUTHORS	Weng Y,DiRusso CC,Reilly AA,Black PN,Ding X
CONTRIBUTOR	John Newman
CONTRIBUTOR_ORG	University of Washington
EXACT_SOURCE	Table 1: Cpr-low/Cpr-lox =< 0.5
FILTERED_BY_SIMILARITY	
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EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AW495875,BF719154,C77384,NM_007468,NM_007825,NM_007913,NM_007980,NM_008175,NM_009014,NM_010003,NM_011396,NM_011704,NM_011844,NM_012006,NM_013559,NM_016763,NM_019750,NM_023737,NM_024255,NM_024433,NM_026159,NM_029494,NM_030693,NM_033369,NM_053262,NM_134188,NM_134255,NM_145594,NM_201640
GENE_SYMBOLS	,,,APOA4,CYP7B1,EGR1,FABP2,GRN,RAD51B,CYP2C19,SLC22A5,VNN1,MGLL,ACOT1,HSPH1,HSD17B10,NAA80,EHHADH,HSDL2,MTAP,RETSAT,RAB30,ATF5,,HSD17B11,ACOT2,ELOVL5,FGL1,CYP4A11
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