Impaired renal Na<sup>+</sup> retention in the <em>sgk1</em>-knockout mouse

Peer Wulff

Volker Vallon

Dan Huang

Harald Völkl

Karin Klingel+5 authors

^{Zentrum für Molekulare Neurobiologie, University of Hamburg, Hamburg, Germany}^{Department of Pharmacology, University of Tübingen, Tübingen, Germany}^{Department of Physiology, University of Innsbruck, Innsbruck, Austria}^{Department of Molecular Pathology, Institute of Pathology, University of Tübingen, Tübingen, Germany}^{Department of Anatomy, University of Zürich, Zürich, Switzerland}^{Department of Physiology, University of Tübingen, Tübingen, Germany}^{Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Berlin, Germany}

Address correspondence to: Dietmar Kuhl, Molecular Neurobiology (Biochemie der Tiere), Department of Biology, Chemistry, and Pharmacy, Free University Berlin, Takustrasse 6, D-14195 Berlin, Germany. Phone: 49-30-8-385-6940; Fax: 49-30-8-385-6943; E-mail: ed.nilreb-uf.eimehc@lhuk.

Received 2002 Apr 16; Accepted 2002 Sep 10.

Abstract

The serum- and glucocorticoid-regulated kinase (sgk1) is induced by mineralocorticoids and, in turn, upregulates heterologously expressed renal epithelial Na^{channel (ENaC) activity in Xenopus oocytes. Accordingly, Sgk1 is considered to mediate the mineralocorticoid stimulation of renal ENaC activity and antinatriuresis. Here we show that at standard NaCl intake, renal water and electrolyte excretion is indistinguishable in}sgk1-knockout (sgk1^–/–) mice and wild-type (sgk1^+/+) mice. In contrast, dietary NaCl restriction reveals an impaired ability of sgk1^–/– mice to adequately decrease Na^{excretion despite increases in plasma aldosterone levels and proximal-tubular Na}^{and fluid reabsorption, as well as decreases in blood pressure and glomerular filtration rate.}

Abstract

Acknowledgments

We thank B. Rossier for ENaC antibodies and S. Berger for valuable discussions. This work was supported by grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung (to D. Kuhl, F. Lang, and V. Vallon), and Schweizer Nationalfonds (to J. Loffing).

Acknowledgments

Footnotes

See the related Commentary beginning on page 1233.

Peer Wulff’s present address is: Department of Clinical Neurobiology, University Hospital of Neurology, Heidelberg, Germany.

Gunther Kauselmann’s present address is: Artemis Pharmaceuticals GmbH, Cologne, Germany.

Conflict of interest: No conflict of interest has been declared.

Nonstandard abbreviations used: epithelial Na^{channel (ENaC); serum- and glucocorticoid-regulated kinase (Sgk1); embryonic stem (ES); glomerular filtration rate (GFR).}

Footnotes

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