title: Evaluation of CMV and KAP promoters for driving the expression of human             CYP4F2 in transgenic mice.
abstract: A transgenic mouse model in which cytochrome P450 4F2 (CYP4F2) was expressed             in multiple organs was expected to clarify the role of 20-hydroxyeicosatetraenoic             acid (20-HETE) in the regulation of blood pressure, compared with our previously             established kidney androgen-regulated protein (KAP) promoter CYP4F2 transgenic             mouse model which predominantly showed renal overexpression of CYP4F2. A novel             CYP4F2 transgenic mouse model driven by the cyto-megalovirus (CMV) promoter was             generated and identified by PCR and subsequent sequencing. Extensive study of             CMV-CYP4F2 transgenic mice demonstrated that CYP4F2 was exclusively expressed             in the liver, while 20-HETE levels in the urine, kidney and blood were not affected,             and there was no resulting change in the systolic blood pressure. This was in             contrast to KAP-CYP4F2 transgenic mice which exerted prohypertensive action of             20-HETE resulting from the renal overexpression of CYP4F2. In addition, CYP4F2             overwhelmed the endogenous renal Cyp4a family mRNA levels in the KAP-CYP4F2 but             not in the CMV-CYP4F2 transgenic mice. These results support the idea that overexpression             of renal CYP4F2, leading to high 20-HETE in the urine and blood, may account for             the elevated blood pressure. The CMV promoter did not direct CYP4F2 expression             into extensive tissues and organs in an attempt to clarify the action of 20-HETE.
authors: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
authors: Guangrui
authors: G
authors: Lai
authors: Xiaoliang
authors: X
authors: Liu
authors: Jingjing
authors: J
authors: Wu
authors: Hong
authors: H
authors: Liu
authors: Yanyan
authors: Y
authors: Zhao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000072470:Cytochrome P450 Family 4; D003587:Cytomegalovirus / Q000235:genetics*; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood / Q000378:metabolism / Q000652:urine; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D011506:Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; C067670:Kap protein, mouse; D020033:Protein Isoforms; D011506:Proteins; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human