Cyp1a2

Summary

Gene Symbol: Cyp1a2
Description: cytochrome P450, family 1, subfamily a, polypeptide 2
Alias: CP12, CYPIA2, P450-3, cytochrome P450 1A2, cholesterol 25-hydroxylase, cytochrome P450 family 1 subfamily a polypeptide 1, cytochrome P450, 1a2, aromatic compound inducible, cytochrome P450-P2, cytochrome P450-P3
Species: mouse
Products:     Cyp1a2

Top Publications

  1. Liang H, Li H, McKinnon R, Duffy J, Potter S, Puga A, et al. Cyp1a2(-/-) null mutant mice develop normally but show deficient drug metabolism. Proc Natl Acad Sci U S A. 1996;93:1671-6 pubmed
    b>Cytochrome P450 1A2 (CYP1A2) is a predominantly hepatic enzyme known to be important in the metabolism of numerous foreign chemicals of pharmacologic, toxicologic, and carcinogenic significance...
  2. Dragin N, Dalton T, Miller M, Shertzer H, Nebert D. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. J Biol Chem. 2006;281:18591-600 pubmed
    ..The Cyp1a1, Cyp1a2, and Cyp1b1 genes are up-regulated by the aryl hydrocarbon receptor...
  3. Nukaya M, Moran S, Bradfield C. The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. Proc Natl Acad Sci U S A. 2009;106:4923-8 pubmed publisher
    ..The Cyp1a1 and Cyp1a2 loci represent linked genes thought to play important roles in AHR biology...
  4. Nebert D, Dalton T, Okey A, Gonzalez F. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem. 2004;279:23847-50 pubmed
    The mammalian CYP1A1, CYP1A2, and CYP1B1 genes (encoding cytochromes P450 1A1, 1A2, and 1B1, respectively) are regulated by the aromatic hydrocarbon receptor (AHR)...
  5. Corcos L, Marc N, Wein S, Fautrel A, Guillouzo A, Pineau T. Phenobarbital induces cytochrome P4501A2 hnRNA, mRNA and protein in the liver of C57BL/6J wild type and aryl hydrocarbon receptor knock-out mice. FEBS Lett. 1998;425:293-7 pubmed
    ..Using the DNA binding site for the aryl hydrocarbon receptor as a probe, gel retardation analyses showed that phenobarbital treatment induced protein binding, regardless of the presence of the aryl hydrocarbon receptor. ..
  6. Diliberto J, Burgin D, Birnbaum L. Role of CYP1A2 in hepatic sequestration of dioxin: studies using CYP1A2 knock-out mice. Biochem Biophys Res Commun. 1997;236:431-3 pubmed
    ..Transgenic mice lacking a cytochrome P450 1A2 gene were used to study the influence of the CYP1A2 gene on the hepatic sequestration and distribution of ..
  7. Gorman N, Ross K, Walton H, Bement W, Szakacs J, Gerhard G, et al. Uroporphyria in mice: thresholds for hepatic CYP1A2 and iron. Hepatology. 2002;35:912-21 pubmed
    ..Here we investigate the development of uroporphyria as a function of CYP1A2 and iron levels in the liver of mice having a common C57BL/6 genetic background...
  8. Diliberto J, Burgin D, Birnbaum L. Effects of CYP1A2 on disposition of 2,3,7, 8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 2,2',4,4',5,5'-hexachlorobiphenyl in CYP1A2 knockout and parental (C57BL/6N and 129/Sv) strains of mice. Toxicol Appl Pharmacol. 1999;159:52-64 pubmed
    ..responsible for this hepatic sequestration of TCDD and its congeners has been shown by our laboratory to be CYP1A2 (J. J. Diliberto, D. Burgin, and L. S. Birnbaum, 1997, Biochem. Biophys. Res. Commun. 236, 431-433)...
  9. Giguere V, Beatty B, Squire J, Copeland N, Jenkins N. The orphan nuclear receptor ROR alpha (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9. Genomics. 1995;28:596-8 pubmed
    ..This places the human RORA gene in the proximity of the PML gene, which is involved in a reciprocal chromosomal translocation t(15:17) with the RARA gene in patients with acute promyelocytic leukemia. ..
  10. Curran C, Nebert D, Genter M, Patel K, Schaefer T, Skelton M, et al. In utero and lactational exposure to PCBs in mice: adult offspring show altered learning and memory depending on Cyp1a2 and Ahr genotypes. Environ Health Perspect. 2011;119:1286-93 pubmed publisher
    ..Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; ..

Detail Information

Publications62

  1. Liang H, Li H, McKinnon R, Duffy J, Potter S, Puga A, et al. Cyp1a2(-/-) null mutant mice develop normally but show deficient drug metabolism. Proc Natl Acad Sci U S A. 1996;93:1671-6 pubmed
    b>Cytochrome P450 1A2 (CYP1A2) is a predominantly hepatic enzyme known to be important in the metabolism of numerous foreign chemicals of pharmacologic, toxicologic, and carcinogenic significance...
  2. Dragin N, Dalton T, Miller M, Shertzer H, Nebert D. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. J Biol Chem. 2006;281:18591-600 pubmed
    ..The Cyp1a1, Cyp1a2, and Cyp1b1 genes are up-regulated by the aryl hydrocarbon receptor...
  3. Nukaya M, Moran S, Bradfield C. The role of the dioxin-responsive element cluster between the Cyp1a1 and Cyp1a2 loci in aryl hydrocarbon receptor biology. Proc Natl Acad Sci U S A. 2009;106:4923-8 pubmed publisher
    ..The Cyp1a1 and Cyp1a2 loci represent linked genes thought to play important roles in AHR biology...
  4. Nebert D, Dalton T, Okey A, Gonzalez F. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem. 2004;279:23847-50 pubmed
    The mammalian CYP1A1, CYP1A2, and CYP1B1 genes (encoding cytochromes P450 1A1, 1A2, and 1B1, respectively) are regulated by the aromatic hydrocarbon receptor (AHR)...
  5. Corcos L, Marc N, Wein S, Fautrel A, Guillouzo A, Pineau T. Phenobarbital induces cytochrome P4501A2 hnRNA, mRNA and protein in the liver of C57BL/6J wild type and aryl hydrocarbon receptor knock-out mice. FEBS Lett. 1998;425:293-7 pubmed
    ..Using the DNA binding site for the aryl hydrocarbon receptor as a probe, gel retardation analyses showed that phenobarbital treatment induced protein binding, regardless of the presence of the aryl hydrocarbon receptor. ..
  6. Diliberto J, Burgin D, Birnbaum L. Role of CYP1A2 in hepatic sequestration of dioxin: studies using CYP1A2 knock-out mice. Biochem Biophys Res Commun. 1997;236:431-3 pubmed
    ..Transgenic mice lacking a cytochrome P450 1A2 gene were used to study the influence of the CYP1A2 gene on the hepatic sequestration and distribution of ..
  7. Gorman N, Ross K, Walton H, Bement W, Szakacs J, Gerhard G, et al. Uroporphyria in mice: thresholds for hepatic CYP1A2 and iron. Hepatology. 2002;35:912-21 pubmed
    ..Here we investigate the development of uroporphyria as a function of CYP1A2 and iron levels in the liver of mice having a common C57BL/6 genetic background...
  8. Diliberto J, Burgin D, Birnbaum L. Effects of CYP1A2 on disposition of 2,3,7, 8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 2,2',4,4',5,5'-hexachlorobiphenyl in CYP1A2 knockout and parental (C57BL/6N and 129/Sv) strains of mice. Toxicol Appl Pharmacol. 1999;159:52-64 pubmed
    ..responsible for this hepatic sequestration of TCDD and its congeners has been shown by our laboratory to be CYP1A2 (J. J. Diliberto, D. Burgin, and L. S. Birnbaum, 1997, Biochem. Biophys. Res. Commun. 236, 431-433)...
  9. Giguere V, Beatty B, Squire J, Copeland N, Jenkins N. The orphan nuclear receptor ROR alpha (RORA) maps to a conserved region of homology on human chromosome 15q21-q22 and mouse chromosome 9. Genomics. 1995;28:596-8 pubmed
    ..This places the human RORA gene in the proximity of the PML gene, which is involved in a reciprocal chromosomal translocation t(15:17) with the RARA gene in patients with acute promyelocytic leukemia. ..
  10. Curran C, Nebert D, Genter M, Patel K, Schaefer T, Skelton M, et al. In utero and lactational exposure to PCBs in mice: adult offspring show altered learning and memory depending on Cyp1a2 and Ahr genotypes. Environ Health Perspect. 2011;119:1286-93 pubmed publisher
    ..Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; ..
  11. Prochazka M, Leiter E, Serreze D, Coleman D. Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. Science. 1987;237:286-9 pubmed
    ....
  12. Pineau T, Fernandez Salguero P, Lee S, McPhail T, Ward J, Gonzalez F. Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2. Proc Natl Acad Sci U S A. 1995;92:5134-8 pubmed
    b>Cytochrome P450 1A2 (CYP1A2) is a constitutively expressed hepatic enzyme that is highly conserved among mammals...
  13. Planas Paz L, Orsini V, Boulter L, Calabrese D, Pikiolek M, Nigsch F, et al. The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size. Nat Cell Biol. 2016;18:467-79 pubmed publisher
    ..Taken together, our results indicate that the RSPO-LGR4/5-ZNRF3/RNF43 module controls metabolic liver zonation and is a hepatic growth/size rheostat during development, homeostasis and regeneration. ..
  14. Gonzalez F, Kimura S. Role of gene knockout mice in understanding the mechanisms of chemical toxicity and carcinogenesis. Cancer Lett. 1999;143:199-204 pubmed
    ..Mouse lines having disruption of genes encoding P450s CYP1A2, CYP2E1, and CYP1B1 were developed by use of gene disruption in empbryonic stem cells...
  15. Hildebrand C, Gonzalez F, Kozak C, Nebert D. Regional linkage analysis of the dioxin-inducible P-450 gene family on mouse chromosome 9. Biochem Biophys Res Commun. 1985;130:396-406 pubmed
    ....
  16. Prochazka M, Serreze D, Worthen S, Leiter E. Genetic control of diabetogenesis in NOD/Lt mice. Development and analysis of congenic stocks. Diabetes. 1989;38:1446-55 pubmed
    ..abstract truncated at 400 words) ..
  17. Uno S, Endo K, Ishida Y, Tateno C, Makishima M, Yoshizato K, et al. CYP1A1 and CYP1A2 expression: comparing 'humanized' mouse lines and wild-type mice; comparing human and mouse hepatoma-derived cell lines. Toxicol Appl Pharmacol. 2009;237:119-26 pubmed publisher
    ..mouse, carrying the human CYP1A1_CYP1A2 locus and lacking the mouse Cyp1a1 and Cyp1a2 orthologs, was shown to express robustly human dioxin-inducible CYP1A1 and basal versus inducible CYP1A2 (mRNAs, ..
  18. Uno S, Dalton T, Dragin N, Curran C, Derkenne S, Miller M, et al. Oral benzo[a]pyrene in Cyp1 knockout mouse lines: CYP1A1 important in detoxication, CYP1B1 metabolism required for immune damage independent of total-body burden and clearance rate. Mol Pharmacol. 2006;69:1103-14 pubmed
    ..To further investigate the mechanism for this enhanced sensitivity, Cyp1a1-/-, Cyp1a2-/-, and Cyp1b1-/- single-knockout, Cyp1a1/1b1-/- and Cyp1a2/1b1-/- double-knockout, and Cyp1+/+ wild-type mice ..
  19. Montagutelli X, Serikawa T, Guenet J. PCR-analyzed microsatellites: data concerning laboratory and wild-derived mouse inbred strains. Mamm Genome. 1991;1:255-9 pubmed
    ..These results emphasize the interest of using Mus musculus musculus inbred strains to establish interspecific crosses, particularly when considering their breeding performances. ..
  20. Kimura S, Gonzalez F, Nebert D. The murine Ah locus. Comparison of the complete cytochrome P1-450 and P3-450 cDNA nucleotide and amino acid sequences. J Biol Chem. 1984;259:10705-13 pubmed
    ....
  21. Lingappan K, Jiang W, Wang L, Couroucli X, Moorthy B. Sex-specific differences in hyperoxic lung injury in mice: role of cytochrome P450 (CYP)1A. Toxicology. 2015;331:14-23 pubmed publisher
    ..Eight week-old male and female wild type (WT) (C57BL/6J) mice, Cyp1a1-/-, and Cyp1a2-/- mice were exposed to 72h of hyperoxia (FiO2>0.95)...
  22. Dalton T, Dieter M, Matlib R, Childs N, Shertzer H, Genter M, et al. Targeted knockout of Cyp1a1 gene does not alter hepatic constitutive expression of other genes in the mouse [Ah] battery. Biochem Biophys Res Commun. 2000;267:184-9 pubmed
    ..In a cultured hepatoma CYP1A1 metabolism-deficient mutant line that does not express Cyp1a2, we have previously shown that constitutive transcriptional up-regulation of other [Ah] gene battery members ..
  23. Casley W, Menzies J, Whitehouse L, Moon T. Detection of quantitative trait loci affecting caffeine metabolism by interval mapping in a genome-wide scan of C3H/HeJ x APN F(2) mice. Drug Metab Dispos. 1999;27:1375-80 pubmed
    ..0) between a locus on chromosome 9, which colocalized with the murine Cyp1a2 locus, and the plasma paraxanthine/caffeine ratio was identified...
  24. Zaher H, Buters J, Ward J, Bruno M, Lucas A, Stern S, et al. Protection against acetaminophen toxicity in CYP1A2 and CYP2E1 double-null mice. Toxicol Appl Pharmacol. 1998;152:193-9 pubmed
    ..At least two forms of cytochrome P450, CYP2E1 and CYP1A2, have been implicated in this reaction in mice...
  25. Stiborova M, Levová K, Bárta F, Shi Z, Frei E, Schmeiser H, et al. Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2. Toxicol Sci. 2012;125:345-58 pubmed publisher
    ..human cytochrome P450 (CYP) 1A1 and 1A2 in two CYP1A-humanized mouse lines that carry functional human CYP1A1 and CYP1A2 genes in the absence of the mouse Cyp1a1/1a2 orthologs...
  26. Brott B, Alessandrini A, Largaespada D, Copeland N, Jenkins N, Crews C, et al. MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues. Cell Growth Differ. 1993;4:921-9 pubmed
    ..Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not. These findings suggest that MEK2 is a member of a multigene family. ..
  27. Uno S, Dragin N, Miller M, Dalton T, Gonzalez F, Nebert D. Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008;44:570-83 pubmed
    The CYP1A1, CYP1A2, and CYP1B1 enzymes are inducible by benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); metabolism of BaP by these enzymes leads to electrophilic intermediates and genotoxicity...
  28. Jiang Z, Dalton T, Jin L, Wang B, Tsuneoka Y, Shertzer H, et al. Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum Mutat. 2005;25:196-206 pubmed
    Interindividual differences in human CYP1A1 and CYP1A2 expression appear to be associated with variability in risk toward various types of environmental toxicity and cancer...
  29. Schleef M, Werner K, Satzger U, Kaupmann K, Jockusch H. Chromosomal localization and genomic cloning of the mouse alpha-tropomyosin gene Tpm-1. Genomics. 1993;17:519-21 pubmed
    ..Using interspecies backcrosses, we have localized Tpm-1 on mouse chromosome 9, cen-Cyp1a2-Tpm-1-Mod-1-Mylc-Scn5a, near the d-se region...
  30. Tomita S, Sinal C, Yim S, Gonzalez F. Conditional disruption of the aryl hydrocarbon receptor nuclear translocator (Arnt) gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1alpha. Mol Endocrinol. 2000;14:1674-81 pubmed
    ..Induction of CYP1A1, CYP1A2, and UGT1*06 mRNAs by the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin was absent in livers of Arnt-floxed/Mx1-..
  31. Nemoto N, Sakurai J. Differences in regulation of gene expression between Cyp1a-1 and Cyp1a-2 in adult mouse hepatocytes in primary culture. Carcinogenesis. 1992;13:2249-54 pubmed
    ..In contrast, while levels of CYP1A2 mRNA in spheroid culture were also appreciable throughout, they rapidly decreased in monolayer culture to become ..
  32. Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman J. Expression patterns of mouse and human CYP orthologs (families 1-4) during development and in different adult tissues. Arch Biochem Biophys. 2005;436:50-61 pubmed
    ..Except for CYP1A2, all of these CYPs exhibited specific patterns of expression during mouse ontogeny, suggesting possible ..
  33. Matysiak Scholze U, Nehls M. The structural integrity of ROR alpha isoforms is mutated in staggerer mice: cerebellar coexpression of ROR alpha1 and ROR alpha4. Genomics. 1997;43:78-84 pubmed
    ..Our finding of cerebellum-specific coregulation suggests that distinct sets of target genes regulated by the ROR alpha1 and ROR alpha4 isoforms are required for Purkinje cell development. ..
  34. Shi Z, Chen Y, Dong H, Amos Kroohs R, Nebert D. Generation of a 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahrd mouse line harboring the poor-affinity aryl hydrocarbon receptor. Biochem Biophys Res Commun. 2008;376:775-80 pubmed publisher
    ..generation of the hCYP1A1_1A2_Cyp1a1/1a2(-/-)_Ahr(d) mouse line, which carries human functional CYP1A1 and CYP1A2 genes in the absence of mouse Cyp1a1 and Cyp1a2 genes, in a (>99...
  35. Hakk H, Diliberto J, Birnbaum L. The effect of dose on 2,3,7,8-TCDD tissue distribution, metabolism and elimination in CYP1A2 (-/-) knockout and C57BL/6N parental strains of mice. Toxicol Appl Pharmacol. 2009;241:119-26 pubmed publisher
    ..A hallmark feature of TCDD exposure is induction of hepatic CYP1A2 and subsequent sequestration leading to high liver-to-fat concentration ratios...
  36. Petersen D, Gonzalez F, Rapic V, Kozak C, Lee J, Jones J, et al. Marked increases in hepatic NAD(P)H:oxidoreductase gene transcription and mRNA levels correlated with a mouse chromosome 7 deletion. Proc Natl Acad Sci U S A. 1989;86:6699-703 pubmed
    ..Conversely, there are no detectable basal levels of cytochrome P1450 (Cyp1a1 gene) or cytochrome P3450 (Cyp1a2 gene) mRNA, indicating that the regulation of basal expression of the Cyp1a1 and Cyp1a2 genes is distinct from ..
  37. Levová K, Moserova M, Nebert D, Phillips D, Frei E, Schmeiser H, et al. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I. Toxicol Appl Pharmacol. 2012;265:360-7 pubmed publisher
    ..We found that NQO1 levels in liver, kidney and lung of Cyp1a1⁻/⁻, Cyp1a2⁻/⁻ and Cyp1a1/1a2⁻/⁻ knockout mouse lines, as well as in two CYP1A-humanized mouse lines harboring ..
  38. Aitchison K, Jann M, Zhao J, Sakai T, Zaher H, Wolff K, et al. Clozapine pharmacokinetics and pharmacodynamics studied with Cyp1A2-null mice. J Psychopharmacol. 2000;14:353-9 pubmed
    The aim of this study was to use the CYP1A2-null mouse to investigate the in-vivo contribution of CYP1A2 to clozapine pharmacokinetics and pharmacodynamics...
  39. Sinclair P, Gorman N, Walton H, Bement W, Dalton T, Sinclair J, et al. CYP1A2 is essential in murine uroporphyria caused by hexachlorobenzene and iron. Toxicol Appl Pharmacol. 2000;162:60-7 pubmed
    Using Cyp1a2(-/-) mice we previously showed that CYP1A2 is absolutely required for hepatic uroporphyrin accumulation caused by iron and 5-aminolevulinate (ALA) treatment, both in the presence and absence of an inducer of CYP1A2...