Developmental and tissue-specific differential regulation of the mouse dioxin-inducible P-450 and P-450 genes

Tuteja, Narendra ; Gonzalez, Frank J. ; Nebert, Daniel W. (1985) Developmental and tissue-specific differential regulation of the mouse dioxin-inducible P-450 and P-450 genes Developmental Biology, 112 (1). pp. 177-184. ISSN 0012-1606

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Official URL: http://www.sciencedirect.com/science/article/pii/0...

Related URL: http://dx.doi.org/10.1016/0012-1606(85)90131-9

Abstract

The murine Ah locus has two structural genes, P1-450 and P3-450, that are members of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible P-450 gene family and are closely linked on mouse chromosome 9. Transcriptional activation of both genes in liver is controlled by the Ah receptor. Inducible P1-450 mRNA is correlated with aryl hydrocarbon hydroxylase activity, whereas inducible P3-450 mRNA is correlated with acetanilide 4-hydroxylase activity. This report shows that inducible P3-450 mRNA is also highly correlated with estradiol 2-hydroxylase activity. Both P1-450 and P3-450 activities are induced by 3-methylcholanthrene in liver; in contrast, P1-450 but not P3-450 activity is induced to a significant extent in kidney, lung, and intestine. Constitutive levels of P3-450 mRNA in liver are at least five times greater than those of P1-450 mRNA, thus accounting for the much greater "fold inducibility" of aryl hydrocarbon hydroxylase than acetanilide 4-hydroxylase or estradiol 2-hydroxylase. The hepatic P3-450 induction response occurs at lower inducer concentrations than the P1-450 induction response, suggesting a difference in affinity of the inducer-receptor complex for regulatory regions of the two genes. Developmentally, P1-450 inducibility occurs at least 2 weeks earlier in gestation than P3-450 inducibility, which occurs near the time of birth. These data thus demonstrate striking differences between the expression of two homologous genes in the same P-450 subfamily, with respect to developmental and tissue specificity and sensitivity to common inducers that interact with the Ah receptor.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
ID Code:52752
Deposited On:04 Aug 2011 11:54
Last Modified:04 Aug 2011 11:54

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