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Null phenotype for cytochrome P450 2B2 in the rat results from a deletion of its structural gene

CJ Omiecinski, R Ramsden, A Rampersaud and FG Walz

Department of Environmental Health, School of Public Health and Community Medicine, University of Washington, Seattle 98195.

The absence of phenobarbital (PB)-inducible cytochrome P450 2B2 (CYP2B2) in hepatic microsomes from Marshall 520 (M520) and Wistar Munich (WM) inbred strains of rat was previously reported [Biochem. Genet. 25:527-534 (1987)], and it was subsequently shown for M520 rats that corresponding CYP2B2 mRNA was not detected in hepatic extracts from either control or PB-treated animals [DNA 8:29-37 (1989)]. In the present study, solution hybridization was used to quantify PB-induced CYP2B2 and CYP2B1 mRNAs in livers from M520, WM, and outbred Sprague- Dawley rats, as well as additional inbred strains that express all known electrophoretic phenotypes for both of these closely related isozymes. Amounts of these mRNAs were also measured for F1 and F2 progenies of crosses involving M520 rats. The results indicated that the extent of PB induction of both isozymes appears to be independent of the electrophoretic phenotype. It was also shown that the null phenotype for CYP2B2 observed in M520 rats results from a mutation of a single autosomal gene and is inherited codominantly, regarding protein and mRNA phenotypes. Analyses of restriction digests and specific polymerase chain reaction products of hepatic DNAs revealed that the basis for the null phenotype of CYP2B2 in M520 and WM rats was a deletion of the CYP2B2 gene.

Volume 42, Issue 2, pp. 249-256, 08/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




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 J. Pharmacol. Exp. Ther.Home page
H. Yamada, H. Matsunaga, K. Tsuji, S. Matsumoto, M. Yamamoto, Y. Ishii, C. J. Omiecinski, and K. Oguri
Sequence Analyses of CYP2B Genes and Catalytic Profiles for P450s in Qdj:Sprague-Dawley Rats That Lack Response to the Phenobarbital-Mediated Induction of CYP2B2
J. Pharmacol. Exp. Ther., December 1, 2000; 295(3): 986 - 993.
[Abstract] [Full Text]


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Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics