A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice

作者:Tanimoto Keiji*; Kanafusa Sumiyo; Ushiki Aki; Matsuzaki Hitomi; Ishida Junji; Sugiyama Fumihiro; Fukamizu Akiyoshi
来源:Journal of Receptors and Signal Transduction, 2014, 34(5): 401-409.
DOI:10.3109/10799893.2014.908917

摘要

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.

  • 出版日期2014-10