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Gene Review

Cyp7a1  -  cytochrome P450, family 7, subfamily a,...

Mus musculus

Synonyms: CYPVII, Cholesterol 7-alpha-hydroxylase, Cholesterol 7-alpha-monooxygenase, Cyp7, Cytochrome P450 7A1, ...
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Disease relevance of Cyp7a1


High impact information on Cyp7a1

  • The synthesis and excretion of bile acids were found to be dramatically elevated in these mutants, and the expression of 2 key bile acid synthase genes, cholesterol 7alpha-hydroxylase (Cyp7a1) and sterol 12alpha-hydroxylase (Cyp8b1), was strongly upregulated [6].
  • Therefore, betaKlotho may stand as a novel contributor to Cyp7a1-selective regulation [6].
  • The expression of Cyp7a1 and Cyp8b1 is known to be repressed by dietary bile acids via both SHP-dependent and -independent regulations [6].
  • None of these loci were linked to the C7AH structural gene which we mapped to proximal chromosome 4 [4].
  • We confirmed previous findings that dietary cholesterol increased mouse Cyp7a1 activity in Het mice but decreased human Cyp7a1 activity in Tg+KO mice [7].

Chemical compound and disease context of Cyp7a1

  • Interestingly, hepatic cholestasis was observed in 100% of the bezafibrate-fed (-/-) mice, and this was accompanied by significantly elevated hepatic expression of mRNA encoding bile salt export pump and lower expression of mRNA encoding cytochrome P450 7A1, consistent with enhanced activation of the bile acid receptor, farnesoid X receptor [8].

Biological context of Cyp7a1

  • Cholesterol feeding increased the expression of the endogenous modified Cyp7a1 allele but failed to stimulate the human CYP7A1 transgene [9].
  • When administered orally to mice, both compounds (BAPA-3>BAPA-6) reduced the bile acid pool size, which was accompanied by up-regulation of hepatic Cyp7a1 and Hmgcr and intestinal Ostalpha/Ostbeta [10].
  • ES cells expressing green fluorescent protein (GFP) under the control of the Cyp7a1 enhancer/promoter showed that cultured EBs contained GFP-positive epithelial-like cells [11].
  • Among the intercross mice, multiple loci contributed to the regulation of C7AH mRNA levels in response to the diet, the most notable of which coincided with the loci on chromosomes 3, 5, and 11 controlling HDL levels in response to the diet [4].
  • Aspects of lipid metabolism in the Cyp7-/- mice are characterized here to deduce the physiological basis of this phenotype [12].

Anatomical context of Cyp7a1


Associations of Cyp7a1 with chemical compounds

  • These results challenge the notion that dietary cholesterol regulation of Cyp7a1 is a major determinant of plasma cholesterol responsiveness [7].
  • Cholesterol 7 alpha-hydroxylase (Cyp7a1) plays a central role in the regulation of bile acid and cholesterol metabolism, and transcription of the gene is controlled by bile acids and hormones acting through a complex interaction with a number of potential steroid-hormone-binding sites [16].
  • Treatment of mice with phenobarbital or TCPOBOP resulted in decreased hepatic mRNA levels of the reported genes down-regulated by CAR, including Cyp7a1 and Pepck [17].
  • Although bile acid pool size contracted markedly in all the Cyp7a1(-/-) mice, the female Cyp7a1(-/-) mice maintained a larger, more cholic acid-rich pool than their male counterparts [18].
  • Bile acid synthesis in Cyp7a1(+/+) males and females was increased 2-fold by cholesterol feeding, and 4-fold by cholestyramine treatment, but was not changed in matching Cyp7a1(-/-) mice by either of these manipulations [18].

Enzymatic interactions of Cyp7a1

  • Cholesterol 7alpha-hydroxylase (Cyp7a1) catalyzes the rate-limiting step in the intrahepatic conversion of cholesterol to bile acids that may have a role in HDL metabolism [19].

Regulatory relationships of Cyp7a1


Other interactions of Cyp7a1

  • Upon short-term (2 days) treatment with leptin, a dose-dependent increase was seen in the SR-BI protein and mRNA, whereas the Cyp7a1 protein and mRNA were reduced [22].
  • Targeted disruption of the HNF1alpha gene results in decreased Cyp1a2, and Cyp2e1 expression, and increased Cyp4a1 and Cyp7a1 expression, suggesting these enzymes are HNF1alpha target genes [23].
  • This was characterized by a reduced expression of Cyp7b1, and elevation of Cyp7a1 and Cyp8b1 expression [24].
  • Intestinal cholesterol absorption in the Cyp7a1(-/-) males fell from 46% to 3%, and in the matching females from 58% to 17% [18].
  • A sensitive solution hybridization assay using autologous cRNA probes was developed with the aim to study the simultaneous regulation of hepatic mRNA levels, on a quantitative basis, for the LDL receptor (LDLr), HMG-CoA reductase, and cholesterol 7 alpha-hydroxylase (Cho-7-hx) in C57BL/6J mice [25].

Analytical, diagnostic and therapeutic context of Cyp7a1


  1. The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the stimulatory effect of their respective ligands on the murine cholesterol 7alpha-hydroxylase gene promoter. Gbaguidi, G.F., Agellon, L.B. Biochim. Biophys. Acta (2002) [Pubmed]
  2. Tumor necrosis factor-alpha-independent downregulation of hepatic cholesterol 7alpha-hydroxylase gene in mice treated with lead nitrate. Kojima, M., Sekikawa, K., Nemoto, K., Degawa, M. Toxicol. Sci. (2005) [Pubmed]
  3. Coordinate regulation of xenobiotic and bile acid homeostasis by pregnane X receptor. Staudinger, J., Liu, Y., Madan, A., Habeebu, S., Klaassen, C.D. Drug Metab. Dispos. (2001) [Pubmed]
  4. Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism. Machleder, D., Ivandic, B., Welch, C., Castellani, L., Reue, K., Lusis, A.J. J. Clin. Invest. (1997) [Pubmed]
  5. Cholesterol 7-hydroxylase knockout mouse: a model for monohydroxy bile acid-related neonatal cholestasis. Arnon, R., Yoshimura, T., Reiss, A., Budai, K., Lefkowitch, J.H., Javitt, N.B. Gastroenterology (1998) [Pubmed]
  6. Impaired negative feedback suppression of bile acid synthesis in mice lacking betaKlotho. Ito, S., Fujimori, T., Furuya, A., Satoh, J., Nabeshima, Y., Nabeshima, Y. J. Clin. Invest. (2005) [Pubmed]
  7. Cholesterol feeding of mice expressing cholesterol 7alpha-hydroxylase increases bile acid pool size despite decreased enzyme activity. Tiemann, M., Han, Z., Soccio, R., Bollineni, J., Shefer, S., Sehayek, E., Breslow, J.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. Role of peroxisome proliferator-activated receptor-alpha (PPARalpha) in bezafibrate-induced hepatocarcinogenesis and cholestasis. Hays, T., Rusyn, I., Burns, A.M., Kennett, M.J., Ward, J.M., Gonzalez, F.J., Peters, J.M. Carcinogenesis (2005) [Pubmed]
  9. Dietary cholesterol fails to stimulate the human cholesterol 7alpha-hydroxylase gene (CYP7A1) in transgenic mice. Agellon, L.B., Drover, V.A., Cheema, S.K., Gbaguidi, G.F., Walsh, A. J. Biol. Chem. (2002) [Pubmed]
  10. Inhibition of the intestinal absorption of bile acids using cationic derivatives: Mechanism and repercussions. Vicens, M., Macias, R.I., Briz, O., Rodriguez, A., El-Mir, M.Y., Medarde, M., Marin, J.J. Biochem. Pharmacol. (2007) [Pubmed]
  11. Expression of the liver-specific gene Cyp7a1 reveals hepatic differentiation in embryoid bodies derived from mouse embryonic stem cells. Asahina, K., Fujimori, H., Shimizu-Saito, K., Kumashiro, Y., Okamura, K., Tanaka, Y., Teramoto, K., Arii, S., Teraoka, H. Genes Cells (2004) [Pubmed]
  12. Disruption of cholesterol 7alpha-hydroxylase gene in mice. II. Bile acid deficiency is overcome by induction of oxysterol 7alpha-hydroxylase. Schwarz, M., Lund, E.G., Setchell, K.D., Kayden, H.J., Zerwekh, J.E., Björkhem, I., Herz, J., Russell, D.W. J. Biol. Chem. (1996) [Pubmed]
  13. Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells. Saito, K., Yoshikawa, M., Ouji, Y., Moriya, K., Nishiofuku, M., Ueda, S., Hayashi, N., Ishizaka, S., Fukui, H. World J. Gastroenterol. (2006) [Pubmed]
  14. 7 alpha-hydroxylation of 27-hydroxycholesterol: biologic role in the regulation of cholesterol synthesis. Martin, K.O., Reiss, A.B., Lathe, R., Javitt, N.B. J. Lipid Res. (1997) [Pubmed]
  15. Expression of cholesterol-7alpha-hydroxylase in murine macrophages prevents cholesterol loading by acetyl-LDL. Moore, G.L., Davis, R.A. J. Lipid Res. (2002) [Pubmed]
  16. The effect of peroxisome-proliferator-activated receptor-alpha on the activity of the cholesterol 7 alpha-hydroxylase gene. Patel, D.D., Knight, B.L., Soutar, A.K., Gibbons, G.F., Wade, D.P. Biochem. J. (2000) [Pubmed]
  17. Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1alpha. Miao, J., Fang, S., Bae, Y., Kemper, J.K. J. Biol. Chem. (2006) [Pubmed]
  18. Alternate pathways of bile acid synthesis in the cholesterol 7alpha-hydroxylase knockout mouse are not upregulated by either cholesterol or cholestyramine feeding. Schwarz, M., Russell, D.W., Dietschy, J.M., Turley, S.D. J. Lipid Res. (2001) [Pubmed]
  19. Cholesterol 7alpha-hydroxylase deficiency in mice on an APOE*3-Leiden background increases hepatic ABCA1 mRNA expression and HDL-cholesterol. Post, S.M., Groenendijk, M., van der Hoogt, C.C., Fievet, C., Luc, G., Hoekstra, M., Princen, H.M., Staels, B., Rensen, P.C. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  20. Redundant pathways for negative feedback regulation of bile acid production. Wang, L., Lee, Y.K., Bundman, D., Han, Y., Thevananther, S., Kim, C.S., Chua, S.S., Wei, P., Heyman, R.A., Karin, M., Moore, D.D. Dev. Cell (2002) [Pubmed]
  21. In vivo regulation of murine CYP7A1 by HNF-6: a novel mechanism for diminished CYP7A1 expression in biliary obstruction. Wang, M., Tan, Y., Costa, R.H., Holterman, A.X. Hepatology (2004) [Pubmed]
  22. Leptin induces the hepatic high density lipoprotein receptor scavenger receptor B type I (SR-BI) but not cholesterol 7alpha-hydroxylase (Cyp7a1) in leptin-deficient (ob/ob) mice. Lundåsen, T., Liao, W., Angelin, B., Rudling, M. J. Biol. Chem. (2003) [Pubmed]
  23. Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha. Maher, J.M., Slitt, A.L., Callaghan, T.N., Cheng, X., Cheung, C., Gonzalez, F.J., Klaassen, C.D. Biochem. Pharmacol. (2006) [Pubmed]
  24. Relationship between hepatic phenotype and changes in gene expression in cytochrome P450 reductase (POR) null mice. Wang, X.J., Chamberlain, M., Vassieva, O., Henderson, C.J., Wolf, C.R. Biochem. J. (2005) [Pubmed]
  25. Hepatic mRNA levels for the LDL receptor and HMG-CoA reductase show coordinate regulation in vivo. Rudling, M. J. Lipid Res. (1992) [Pubmed]
  26. Okara, soybean residue, prevents obesity in a diet-induced murine obesity model. Matsumoto, K., Watanabe, Y., Yokoyama, S. Biosci. Biotechnol. Biochem. (2007) [Pubmed]
  27. Inhibition of cholesterol 7 alpha-hydroxylase by an antibody to a male-specific form of cytochrome P-450 from subfamily P450IIC. Eldredge, E.R., Jackson, B., Suckling, K.E., Wolf, C.R. Biochem. J. (1989) [Pubmed]
  28. Transgenic expression of cholesterol-7-alpha-hydroxylase prevents atherosclerosis in C57BL/6J mice. Miyake, J.H., Duong-Polk, X.T., Taylor, J.M., Du, E.Z., Castellani, L.W., Lusis, A.J., Davis, R.A. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
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