TY - JOUR
T1 - A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice
AU - Tanimoto, Keiji
AU - Kanafusa, Sumiyo
AU - Ushiki, Aki
AU - Matsuzaki, Hitomi
AU - Ishida, Junji
AU - Sugiyama, Fumihiro
AU - Fukamizu, Akiyoshi
N1 - Publisher Copyright:
© 2014 Informa Healthcare USA, Inc.
PY - 2014/7/21
Y1 - 2014/7/21
N2 - 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 TgBAC: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.
AB - 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 TgBAC: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.
KW - Bacterial artificial chromosome
KW - Blood pressure
KW - Renin
KW - Transcriptional regulation
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=84907219207&partnerID=8YFLogxK
U2 - 10.3109/10799893.2014.908917
DO - 10.3109/10799893.2014.908917
M3 - Article
C2 - 24734888
AN - SCOPUS:84907219207
SN - 1079-9893
VL - 34
SP - 401
EP - 409
JO - Journal of Receptors and Signal Transduction
JF - Journal of Receptors and Signal Transduction
IS - 5
ER -