Wu Lin, Gu Jun, Weng Yan, Kluetzman Kerri, Swiatek Pam, Behr Melissa, Zhang Qing-Yu, Zhuo Xiaoliang, Xie Qiang, Ding Xinxin
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.
Genesis. 2003 Aug;36(4):177-81. doi: 10.1002/gene.10214.
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.
NADPH-细胞色素P450还原酶（CPR或POR）是所有微粒体细胞色素P450（CYP或P450）催化的单加氧酶反应的必需电子供体。据报道，小鼠Cpr基因的破坏会导致产前发育缺陷和胚胎致死率。在本研究中，我们构建了一个带有floxed Cpr等位基因的小鼠模型（称为Cpr(lox)）。纯合Cpr(lox)小鼠可育，没有任何组织学异常或CPR表达的任何变化。随后，通过将Cpr(lox)小鼠与具有肝脏特异性Cre表达的转基因小鼠（Alb-Cre）杂交，有效地删除了floxed Cpr等位基因；结果是肝脏微粒体中CPR蛋白水平降低。Cpr(lox)品系对于条件性Cpr基因缺失以及随后确定CPR缺失对内源性和外源性化合物代谢、产后发育和其他生物学功能的影响将具有重要价值。
