Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel

Details

Serval ID
serval:BIB_C019CA31E6AD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Pradervand S., Barker P. M., Wang Q., Ernst S. A., Beermann F., Grubb B. R., Burnier M., Schmidt A., Bindels R. J., Gatzy J. T., Rossier B. C., Hummler E.
ISSN
0027-8424
Publication state
Published
Issued date
02/1999
Peer-reviewed
Oui
Volume
96
Number
4
Pages
1732-37
Notes
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb 16
Abstract
The amiloride-sensitive epithelial sodium channel (ENaC) is a heteromultimer of three homologous subunits (alpha-, beta-, and gamma-subunits). To study the role of the beta-subunit in vivo, we analyzed mice in which the betaENaC gene locus was disrupted. These mice showed low levels of betaENaC mRNA expression in kidney (approximately 1%), lung (approximately 1%), and colon (approximately 4%). In homozygous mutant betaENaC mice, no betaENaC protein could be detected with immunofluorescent staining. At birth, there was a small delay in lung-liquid clearance that paralleled diminished amiloride-sensitive Na+ absorption in tracheal explants. With normal salt intake, these mice showed a normal growth rate. However, in vivo, adult betaENaC m/m mice exhibited a significantly reduced ENaC activity in colon and elevated plasma aldosterone levels, suggesting hypovolemia and pseudohypoaldosteronism type 1. This phenotype was clinically silent, as betaENaC m/m mice showed no weight loss, normal plasma Na+ and K+ concentrations, normal blood pressure, and a compensated metabolic acidosis. On low-salt diets, betaENaC-mutant mice developed clinical symptoms of an acute pseudohypoaldosteronism type 1 (weight loss, hyperkalemia, and decreased blood pressure), indicating that betaENaC is required for Na+ conservation during salt deprivation.
Keywords
Aldosterone/blood Amiloride/pharmacology Animals Blood Pressure Body Weight Colon/metabolism *Diet, Sodium-Restricted Epithelial Sodium Channel Genomic Library Genotype Homozygote Kidney/metabolism Liver/metabolism Lung/metabolism/physiopathology Mice Mice, Knockout Pseudohypoaldosteronism/*genetics/physiopathology Sodium/*metabolism Sodium Channels/*deficiency/genetics/metabolism Trachea/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:00
Last modification date
20/08/2019 15:34
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