Portal de Periódicos da CAPES

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

1999; National Academy of Sciences; Volume: 96; Issue: 4 Linguagem: Inglês

10.1073/pnas.96.4.1727

1091-6490

Fiona J. McDonald, Baoli Yang, Ron F. Hrstka, Heather A. Drummond, D. Ellen K. Tarr, Paul B. McCray, John B. Stokes, Michael J. Welsh, Roger A. Williamson,

Ion channel regulation and function

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.