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First published on October 9, 2008; DOI: 10.1124/dmd.108.023812

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Steven N Hart
Yue Cui
Curtis D. Klaassen
Xiao-bo Zhong
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Received for publication August 26, 2008.
Revised October 3, 2008.
Accepted for publication October 6, 2008.

THREE PATTERNS OF CYTOCHROME P450 GENE EXPRESSION DURING LIVER MATURATION IN MICE

Steven N Hart 1, Yue Cui 1, Curtis D. Klaassen 1, Xiao-bo Zhong 1*

1 University of Kansas Medical Center

* Address correspondence to: E-mail: xzhong{at}kumc.edu

Abstract

The neonatal period of liver development is an often overlooked phase of development. For instance, ontogeny of xenobiotic metabolizing enzymes can markedly affect biotransformation as the liver matures. To systematically examine the ontogenic gene expression patterns of cytochrome P450 genes (Cyps) in mice, the gene expression profiles of 19 xenobiotic metabolizing Cyps in Cyp1-4 families were determined. The mRNA levels in C57BL/6 mouse livers were quantified using branched DNA technology at the following ages: gestational day 17 (2 days before birth), and postnatal days 0, 1, 3, 5, 10, 15, 20, 30, and 45. Among the 13 Cyp genes expressed in mouse livers, three distinct ontogenic expression patterns were identified by cluster analysis. Genes in Group 1 (Cyp3a16 as well as 3a41b in male) were expressed in the perinatal period, but were essentially non-detectable by 30 days of age. Genes in Group 2 (Cyp2e1, 3a11, and 4a10 as well as 3a41b in female) quickly increased after birth and reached maximum expression levels by day 5. Genes in Group 3 (Cyp1a2, 2a4, 2b10, 2c29, 2d22, 2f2, 3a13, and 3a25) were expressed at low levels until day 10-15, but markedly increased at day 20 to a high and stable level. In conclusion, the developmental expression of Cyps in mouse liver can be divided into three patterns, suggesting different mechanisms responsible for the expression of Cyps during liver maturation.


Key words: CYP expression, CYP gene regulation, cytochrome P450, developmental pharmacology


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Y. Li, Y. Cui, S. N. Hart, C. D. Klaassen, and X.-b. Zhong
Dynamic Patterns of Histone Methylation Are Associated with Ontogenic Expression of the Cyp3a Genes during Mouse Liver Maturation
Mol. Pharmacol., May 1, 2009; 75(5): 1171 - 1179.
[Abstract] [Full Text] [PDF]


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