Disruption of the β subunit of the epithelial Na+ channel in mice: Hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype

FJ McDonald, B Yang, RF Hrstka… - Proceedings of the …, 1999 - National Acad Sciences
FJ McDonald, B Yang, RF Hrstka, HA Drummond, DE Tarr, PB McCray Jr, JB Stokes…
Proceedings of the National Academy of Sciences, 1999National Acad Sciences
The epithelial Na+ channel (ENaC) is composed of three homologous subunits: α, β and γ.
We used gene targeting to disrupt the β subunit gene of ENaC in mice. The βENaC-deficient
mice showed normal prenatal development but died within 2 days after birth, most likely of
hyperkalemia. In the−/− mice, we found an increased urine Na+ concentration despite
hyponatremia and a decreased urine K+ concentration despite hyperkalemia. Moreover,
serum aldosterone levels were increased. In contrast to αENaC-deficient mice, which die …
The epithelial Na+ channel (ENaC) is composed of three homologous subunits: α, β and γ. We used gene targeting to disrupt the β subunit gene of ENaC in mice. The βENaC-deficient mice showed normal prenatal development but died within 2 days after birth, most likely of hyperkalemia. In the −/− mice, we found an increased urine Na+ concentration despite hyponatremia and a decreased urine K+ concentration despite hyperkalemia. Moreover, serum aldosterone levels were increased. In contrast to αENaC-deficient mice, which die because of defective lung liquid clearance, neonatal βENaC deficient mice did not die of respiratory failure and showed only a small increase in wet lung weight that had little, if any, adverse physiologic consequence. The results indicate that, in vivo, the β subunit is required for ENaC function in the renal collecting duct, but, in contrast to the α subunit, the β subunit is not required for the transition from a liquid-filled to an air-filled lung. The phenotype of the βENaC-deficient mice is similar to that of humans with pseudohypoaldosteronism type 1 and may provide a useful model to study the pathogenesis and treatment of this disorder.
National Acad Sciences