title: A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice.
abstract: Renin is predominantly expressed in juxtaglomerular cells in the kidney and regulates blood pressure homeostasis. To examine possible in vivo functions of a mouse distal enhancer (mdE), we generated transgenic mice (TgM) carrying either wild-type or mdE-deficient renin BACs (bacterial artificial chromosome), integrated at the identical chromosomal site. In the kidneys of the TgM, the mdE contributed 80% to basal renin promoter activity. To test for possible physiological roles for the mdE, renin BAC transgenes were used to rescue the hypotensive renin-null mice. Interestingly, renal renin expression in the Tg(BAC):renin-null compound mice was indistinguishable between the wild-type and mutant BAC carriers. Surprisingly, however, the plasma renin activity and angiotensin I concentration in the mdE compound mutant mice were significantly lower than the same parameters in the control mice, and the mutants were consistently hypotensive, demonstrating that blood pressure homeostasis is regulated through transcriptional cis elements controlling renin activity.
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba , Tsukuba, Ibaraki , Japan .
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Kanafusa
authors.forename: Aki
authors.initials: A
authors.lastname: Ushiki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Junji
authors.initials: J
authors.lastname: Ishida
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Sugiyama
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012083:Renin / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D012083:Renin
keywords: Bacterial artificial chromosome; blood pressure; renin; transcriptional regulation; transgenic mice