Hummler E Barker P Talbot C Wang Q Verdumo C Grubb B Gatzy J Burnier M Horisberger JD Beermann F Boucher R Rossier BC 1997 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. application/pdf https://sonar.ch/global/documents/277718 eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.94.21.11710 info:eu-repo/semantics/altIdentifier/pmid/9326675 info:eu-repo/semantics/openAccess Proceedings of the National Academy of Sciences of the United States of America. - 1997 Amiloride Animals Animals, Newborn Disease Models, Animal Electrophysiology Epithelial Sodium Channels Fetal Death Genes, Recessive Heterozygote Humans Kidney Lung Membrane Potentials Mice Mice, Knockout Mice, Transgenic Mucous Membrane Pseudohypoaldosteronism Sodium Channels Survival Rate A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism. http://purl.org/coar/resource_type/c_6501