Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype.

Détails

ID Serval
serval:BIB_7ADEF5A6D2A0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype.
Périodique
American Journal of Physiology. Renal Physiology
Auteur(s)
Faresse N., Lagnaz D., Debonneville A., Ismailji A., Maillard M., Fejes-Toth G., Náray-Fejes-Tóth A., Staub O.
ISSN
1522-1466 (Electronic)
ISSN-L
1522-1466
Statut éditorial
Publié
Date de publication
2012
Volume
302
Numéro
8
Pages
F977-F985
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
The expression of the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by mineralocorticoids and, in turn, upregulates the renal epithelial Na(+) channel (ENaC). Total inactivation of Sgk1 has been associated with transient urinary Na(+) wasting with a low-Na(+) 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(+) diet, renal water and Na(+)/K(+) 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(+) increased significantly with a low-salt diet despite higher plasma aldosterone levels. On a low-Na(+) 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(+)-Cl(-)-cotransporter (NCC) and to a lesser extent of ENaC.
Pubmed
Web of science
Création de la notice
12/05/2012 9:55
Dernière modification de la notice
20/10/2020 11:08
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