A transgenic mouse expressing human CYP4B1 in the liver.
The human CYP4B1 protein was expressed in the liver of a transgenic mouse line 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 typical substrate for CYP4B1, to mutagenic compounds detected by an umu gene expression assay. These activities observed in transgenic mouse were efficiently 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 protein of CYP4B1 and NADPH-P450 reductase was expressed in yeast cells. It was able to activate 2-AF and was also able to catalyze omega-hydroxylation of lauric acid. This transgenic mouse line and the recombinant fusion protein provide a useful tool to study human CYP4B1 and its relation to chemical toxicity and carcinogenesis.
Imaoka
S
S
Department of Chemical Biology, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka, Japan. imaoka@med.osaka-cu.ac.jp
Hayashi
K
K
Hiroi
T
T
Yabusaki
Y
Y
Kamataki
T
T
Funae
Y
Y
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005449:Fluorenes / Q000378:metabolism; D006801:Humans; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008862:Microsomes, Liver / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014162:Transfection
D005449:Fluorenes; D007850:Lauric Acids; D011993:Recombinant Fusion Proteins; C030358:lauric acid; C012177:2-aminofluorene; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C095029:cytochrome P-450 CYP4B1; D009251:NADPH-Ferrihemoprotein Reductase