Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type

Nobuyuki Takahashi, Maria Luisa S.Sequeira Lopez, John E. Cowhig, Melissa A. Taylor, Tomoko Hatada, Emily Riggs, Gene Lee, R. Ariel Gomez, Hyung Suk Kim, Oliver Smithies

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

Abstract

Mice lacking Ren1c were generated using C57BL/6-derived embryonic stem cells. Mice homozygous for Ren1c disruption (Ren1c-/-) are born at the expected ratio, but approximately 80% die of dehydration within a few days. The surviving Ren1c-/- mice have no renin mRNA expression in the kidney, hydronephrosis, thickening of renal arterial walls, and fibrosis in the kidney. Plasma renin and angiotensins I and II are undetectable. Urinary aldosterone is 6% wild-type. They have low tail-cuff BP (84 ± 4 versus 116 ± 5 mmHg in +/+) and excrete large amounts of urine (5.2 ± 0.8 ml/d, 725 ± 34 mOsm versus 1.1 ± 0.1 ml/d, 2460 ± 170 mOsm in +/+). After 5 d of drinking 5% dextrose, desmopressin does not increase the osmolality of the urine in -/- mice (624 ± 19 to 656 ± 25 mOsm), whereas in +/+, it increases severalfold (583 ± 44 to 2630 ± 174 mOsm). Minipump infusion of angiotensin II to Ren1c-/- mice restores BP to wild-type level, but preexisting damage to the medulla prevents complete restoration of the ability of the kidney to concentrate urine. Heterozygous Ren1c+/- mice, in contrast, are indistinguishable from +/+ in BP, urine volume, and osmolality. Kidney renin mRNA, the number of kidney cells producing renin, and plasma renin concentration in the Ren1c+/- mice are also indistinguishable from +/+. These results demonstrate that renin is the only enzyme capable of maintaining plasma angiotensins and that renin expression in the kidney is very tightly regulated at the mRNA level.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalJournal of the American Society of Nephrology
Volume16
Issue number1
DOIs
Publication statusPublished - 2005
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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