A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism

Détails

ID Serval
serval:BIB_0959ECAEEC92
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Hummler E., Barker P., Talbot C., Wang Q., Verdumo C., Grubb B., Gatzy J., Burnier M., Horisberger J. D., Beermann F., Boucher R., Rossier B. C.
ISSN
0027-8424 (Print)
Statut éditorial
Publié
Date de publication
10/1997
Volume
94
Numéro
21
Pages
11710-15
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. --- Old month value: Oct 14
Résumé
Aldosterone-dependent epithelial sodium transport in the distal nephron is mediated by the absorption of sodium through the highly selective, amiloride-sensitive epithelial sodium channel (ENaC) made of three homologous subunits (alpha, beta, and gamma). In human, autosomal recessive mutations of alpha, beta, or gammaENaC subunits cause pseudohypoaldosteronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldosterone, hyponatremia, life-threatening hyperkaliemia, and metabolic acidosis. In the mouse, inactivation of alphaENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype. Transgenic expression of alphaENaC driven by a cytomegalovirus promoter in alphaENaC(-/-) knockout mice [alphaENaC(-/-)Tg] rescued the perinatal lethal pulmonary phenotype and partially restored Na+ transport in renal, colonic, and pulmonary epithelia. At days 5-9, however, alphaENaC(-/-)Tg mice showed clinical features of severe PHA-1 with metabolic acidosis, urinary salt-wasting, growth retardation, and 50% mortality. Adult alphaENaC(-/-)Tg survivors exhibited a compensated PHA-1 with normal acid/base and electrolyte values but 6-fold elevation of plasma aldosterone compared with wild-type littermate controls. We conclude that partial restoration of ENaC-mediated Na+ absorption in this transgenic mouse results in a mouse model for PHA-1.
Mots-clé
Amiloride/pharmacology Animals Animals, Newborn Disease Models, Animal Electrophysiology Epithelial Sodium Channel Fetal Death Genes, Recessive Heterozygote Humans Kidney/pathology/physiopathology Lung/pathology/physiology/*physiopathology Membrane Potentials/drug effects/physiology Mice Mice, Knockout Mice, Transgenic Mucous Membrane/drug effects/physiology/physiopathology Pseudohypoaldosteronism/*genetics/pathology/*physiopathology Sodium Channels/biosynthesis/*deficiency/*genetics Survival Rate
Pubmed
Web of science
Création de la notice
24/01/2008 13:38
Dernière modification de la notice
03/03/2018 13:31
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