标题：Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the β-subunit of the amiloride-sensitive epithelial sodium channel
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：4
页码：1732-1737
DOI：10.1073/pnas.96.4.1732
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The amiloride-sensitive epithelial sodium channel (ENaC) is a heteromultimer of three homologous subunits (-, {beta}-, and {gamma}-subunits). To study the role of the {beta}-subunit in vivo, we analyzed mice in which the {beta}ENaC gene locus was disrupted. These mice showed low levels of {beta}ENaC mRNA expression in kidney ({approx}1%), lung ({approx}1%), and colon ({approx}4%). In homozygous mutant {beta}ENaC mice, no {beta}ENaC 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 {beta}ENaC 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 {beta}ENaC 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, {beta}ENaC-mutant mice developed clinical symptoms of an acute pseudohypoaldosteronism type 1 (weight loss, hyperkalemia, and decreased blood pressure), indicating that {beta}ENaC is required for Na+ conservation during salt deprivation.
