Conditional knockout of the mouse NADPH-cytochrome p450 reductase gene.
NADPH-cytochrome P450 reductase (CPR or POR) is the obligatory electron donor for all microsomal cytochrome P450 (CYP or P450)-catalyzed monooxygenase reactions. Disruption of the mouse Cpr gene has been reported to cause prenatal developmental defects and embryonic lethality. In this study, we generated a mouse model with a floxed Cpr allele (termed Cpr(lox)). Homozygous Cpr(lox) mice are fertile and without any histological abnormality or any change in CPR expression. The floxed Cpr allele was subsequently deleted efficiently by crossing Cpr(lox) mice with transgenic mice having liver-specific Cre expression (Alb-Cre); the result was a decrease in the level of CPR protein in liver microsomes. The Cpr(lox) strain will be valuable for conditional Cpr gene deletion and subsequent determination of the impact of CPR loss on the metabolism of endogenous and xenobiotic compounds, as well as on postnatal development and other biological functions.
Wu
Lin
L
Wadsworth Center, New York State Department of Health; and School of Public Health, State University of New York at Albany, Albany, New York 12001, USA.
Gu
Jun
J
Weng
Yan
Y
Kluetzman
Kerri
K
Swiatek
Pam
P
Behr
Melissa
M
Zhang
Qing-Yu
QY
Zhuo
Xiaoliang
X
Xie
Qiang
Q
Ding
Xinxin
X
D000483:Alleles; D000818:Animals; D015139:Blotting, Southern; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D006720:Homozygote; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014018:Tissue Distribution
D009251:NADPH-Ferrihemoprotein Reductase