New elements in human renin promoter involved in cell-specific expression

Clinical and Experimental Pharmacology & Physiology
S GermainF Pinet

Abstract

1. The renin-angiotensin system plays a major role in blood pressure regulation and electrolyte homeostasis through the action of angiotensin (Ang) II. The first and rate-limiting step in the production of AngII is the conversion of angiotensinogen into AngI, which is catalysed by the aspartyl protease renin (EC 3.4.23.15). Circulating active renin is mainly synthesized, processed and secreted by the juxtaglomerular cells within the kidney. 2. To determine the renin 5'-flanking sequences involved in cell and tissue specificity, ex vivo and in vivo studies were performed. Several constructs of various lengths of renin promoter linked to the luciferase gene were first tested ex vivo by transfection in primary cultures of human chorionic cells. The constructs giving a high and specific expression in renin-producing cells were then tested in vivo in a transgenic mice model. 3. The reporter gene chosen to generate transgenic mice was LacZ and the screening was performed in embryos at the embryonic day (E) 15 stage, at which mouse renin is expressed in the developing vessels of the kidney. 4. Only constructs containing more than 5.7 kb of the human renin promoter lead to specific expression of beta-galactosidase in the kidney. 5. Our...Continue Reading

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Citations

Mar 31, 2010·Transgenic Research·Daniel F CarlsonScott C Fahrenkrug

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