{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:02:52Z","timestamp":1792029772863,"version":"4.4.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:p> The expression of the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by mineralocorticoids and, in turn, upregulates the renal epithelial Na<jats:sup>+<\/jats:sup> channel (ENaC). Total inactivation of Sgk1 has been associated with transient urinary Na<jats:sup>+<\/jats:sup> wasting with a low-Na<jats:sup>+<\/jats:sup> diet, while the aldosterone-mediated ENaC channel activation was unchanged in the collecting duct. Since Sgk1 is ubiquitously expressed, we aimed to study the role of renal Sgk1 and generated an inducible kidney-specific knockout (KO) mouse. We took advantage of the previously described TetOn\/CreLoxP system, in which rtTA is under the control of the Pax8 promotor, allowing inducible inactivation of the floxed Sgk1 allele in the renal tubules (Sgk1fl\/fl\/Pax8\/LC1 mice). We found that under a standard Na<jats:sup>+<\/jats:sup> diet, renal water and Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> excretion had a tendency to be higher in doxycycline-treated Sgk1 KO mice compared with control mice. The impaired ability of Sgk1 KO mice to retain Na<jats:sup>+<\/jats:sup> increased significantly with a low-salt diet despite higher plasma aldosterone levels. On a low-Na<jats:sup>+<\/jats:sup> diet, the Sgk1 KO mice were also hyperkaliuric and lost body weight. This phenotype was accompanied by a decrease in systolic and diastolic blood pressure. At the protein level, we observed a reduction in phosphorylation of the ubiquitin protein-ligase Nedd4-2 and a decrease in the expression of the Na<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup>-cotransporter (NCC) and to a lesser extent of ENaC. <\/jats:p>","DOI":"10.1152\/ajprenal.00535.2011","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T20:45:44Z","timestamp":1328215544000},"page":"F977-F985","source":"Crossref","is-referenced-by-count":88,"title":["Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype"],"prefix":"10.1152","volume":"302","author":[{"given":"Nourdine","family":"Faresse","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Lausanne and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmara","family":"Lagnaz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Lausanne 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