Tissue Distribution and Gender-Divergent Expression of 78 Cytochrome P450 mRNAs in Mice
Open Access
- 13 September 2011
- journal article
- research article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 124 (2), 261-277
- https://doi.org/10.1093/toxsci/kfr240
Abstract
Cytochrome P450 (Cyp) enzymes from the first four families (Cyp1–4) play a major role in metabolizing xenobiotics, affecting drug pharmacokinetics and chemical-induced toxicity. Due to cloning of the mouse genome, many novel Cyp isoforms have been identified, but their tissue distribution of expression is unknown. This study compared the tissue distribution of all 78 Cyps from the Cyp1–4 families in C57BL/6 mice providing not only an indication of which tissues novel Cyps may have their greatest importance but also a cohesive comparison of the tissue distribution of all Cyp1–4 isoforms. Transcripts of the 78 Cyps were quantified by multiplex suspension arrays and quantitative real-time PCR in 14 tissues. Hierarchical clustering indicated that in male mice, 52% of the Cyp species were expressed highest in liver, 10% in kidney, 10% in duodenum/jejunum, 10% in testes, 5% in lung, and < 4% in colon, brain, heart, and stomach. Female mice had a similar pattern of Cyp messenger RNA expression; however, compared with males, females had 7% more Cyps that were liver predominant, 2% more Cyps that were stomach predominant, but 1% less Cyps that were kidney and lung predominant. Differences in gender expression were observed in 29 of the Cyps, with 24 being higher in females than males. Additionally, the data suggest a correlation between the spatial arrangement of genes within a gene cluster and their organ-predominant expression, indicating a common regulatory mechanism may be present within these clusters. In conclusion, this study provides novel data on the tissue distribution and gender-divergent expression of 78 functional mouse Cyp isoforms.Keywords
This publication has 61 references indexed in Scilit:
- Tissue Distribution, Ontogeny, and Hormonal Regulation of Xenobiotic Transporters in Mouse KidneysDrug Metabolism and Disposition, 2009
- Sex Differences in the Expression of Hepatic Drug Metabolizing EnzymesPublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2009
- Regulation of Human CYP2C18 and CYP2C19 in Transgenic Mice: Influence of Castration, Testosterone, and Growth HormoneDrug Metabolism and Disposition, 2009
- Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR)Toxicology, 2009
- Tissue Distribution, Gender-Divergent Expression, Ontogeny, and Chemical Induction of Multidrug Resistance Transporter Genes (Mdr1a,Mdr1b,Mdr2) in MicePublished by American Society for Pharmacology & Experimental Therapeutics (ASPET) ,2008
- Prominent Expression of Xenobiotic Efflux Transporters in Mouse Extraembryonic Fetal Membranes Compared with PlacentaDrug Metabolism and Disposition, 2008
- Loss of Sexually Dimorphic Liver Gene Expression upon Hepatocyte-Specific Deletion of Stat5a-Stat5b LocusEndocrinology, 2007
- Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formationBiochemical Journal, 2007
- Gender-specific induction of cytochrome P450s in nonylphenol-treated FVB/NJ miceToxicology and Applied Pharmacology, 2006
- Initial sequencing and comparative analysis of the mouse genomeNature, 2002