A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism

摘要

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 (α, β, and γ). In human, autosomal recessive mu- tations of α, β, or γENaC subunits cause pseudohypoaldo- steronism type 1 (PHA-1), a renal salt-wasting syndrome characterized by severe hypovolemia, high plasma aldoste- rone, hyponatremia, life-threatening hyperkaliemia, and met- abolic acidosis. In the mouse, inactivation of αENaC results in failure to clear fetal lung liquid at birth and in early neonatal death, preventing the observation of a PHA-1 renal phenotype.