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

Keiji Tanimoto, Sumiyo Kanafusa, Aki Ushiki, Hitomi Matsuzaki, Junji Ishida, Fumihiro Sugiyama, Akiyoshi Fukamizu

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)401-409
Number of pages9
JournalJournal of Receptors and Signal Transduction
Volume34
Issue number5
DOIs
Publication statusPublished - Jul 21 2014
Externally publishedYes

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Bacterial Artificial Chromosomes
Blood pressure
Chromosomes
Renin
Homeostasis
Blood Pressure
Kidney
Transgenic Mice
Angiotensin I
Transgenes
Plasmas

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice. / Tanimoto, Keiji; Kanafusa, Sumiyo; Ushiki, Aki; Matsuzaki, Hitomi; Ishida, Junji; Sugiyama, Fumihiro; Fukamizu, Akiyoshi.

In: Journal of Receptors and Signal Transduction, Vol. 34, No. 5, 21.07.2014, p. 401-409.

Research output: Contribution to journalArticle

Tanimoto, Keiji ; Kanafusa, Sumiyo ; Ushiki, Aki ; Matsuzaki, Hitomi ; Ishida, Junji ; Sugiyama, Fumihiro ; Fukamizu, Akiyoshi. / A mouse renin distal enhancer is essential for blood pressure homeostasis in BAC-rescued renin-null mutant mice. In: Journal of Receptors and Signal Transduction. 2014 ; Vol. 34, No. 5. pp. 401-409.
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AU - Ishida, Junji

AU - Sugiyama, Fumihiro

AU - Fukamizu, Akiyoshi

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