A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice. (October 2014)

• Record Type: Journal Article
• Authors: Tanimoto, Keiji; Kanafusa, Sumiyo; Ushiki, Aki; Matsuzaki, Hitomi; Ishida, Junji; Sugiyama, Fumihiro; Fukamizu, Akiyoshi
• Is Part Of: Journal of receptor and signal transduction research. Volume 34:Number 5(2014)
• Page Start: 401
• Page End: 409
• Publication Date: 2014-10
• Subjects: Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.3109/10799893.2014.908917
• Languages: English
• ISSNs: 1079-9893

Abstract

<abstract> <title>Abstract</title> <p>Renin is predominantly expressed in juxtaglomerular cells in the kidney and regulates blood pressure homeostasis. To examine possible <italic>in vivo</italic> 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 <italic>renin</italic>-null mice. Interestingly, renal renin expression in the Tg^BAC:<italic>renin</italic>-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 <italic>cis</italic> elements controlling renin activity.</p> </abstract>