J Biol Chem 2006 Oct 20;281(42):31753-61. Epub 2006 Au
Adams, DJ; Arends, MJ; Head, GA; Kontgen, F; Lovicu, FJ; Markus, MA; Mayorov, DN; Morris, BJ.; Thiru, S; van, der Weyden L
School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
The important cardiovascular regulator renin contains a strong in vitro enhancer 2.7 kb upstream of its gene. Here we tested the in vivo role of the mouse Ren-1c enhancer. In renin-expressing As4.1 cells stably transfected with Ren-1c promoter with or without enhancer, expression of linked beta-geo reporter, stable expression, and colony formation were dependent on the presence of the enhancer. We then generated mice carrying a targeted deletion of the enhancer (REKO mice) and found marked depletion of renin in renal juxtaglomerular and submandibular ductal cells, as well as hyperplasia of macula densa cells. Plasma creatinine was increased, but electrolytes were normal. Male REKO mice implanted with telemetry devices had 9 +/- 1 mm Hg lower mean arterial pressure (p