A transgenic mouse expressing human CYP4B1 in the liver

The human CYP4B1 protein was expressed in the liver of a transgenic mouse l ine under the control of the promoter of the human apolipoprotein E (apo E) gene. Hepatic microsomes of transgenic mice catalyzed omega -hydroxylation of lauric acid and also activated 2-aminofluorene (2-AF), which is a typic al substrate for CYP4B1, to mutagenic compounds detected by an umu gene exp ression assay. These activities observed in transgenic mouse were efficient ly inhibited by CYP4B1 antibody. However, such inhibition was not observed in control mice. This is the first report to indicate catalytic activities of human CYP4B1, For further characterization of human CYP4B1, a fusion pro tein of CYP4B1 and NADPH-P450 reductase was expressed in yeast cells. It wa s able to activate 2-AF and was also able to catalyze omega -hydroxylation of lauric acid. This transgenic mouse line and the recombinant fusion prote in provide a useful tool to study human CYP4B1 and its relation to chemical toxicity and carcinogenesis. (C) 2001 Academic Press.