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

被引:196
作者
McDonald, FJ
Yang, BL
Hrstka, RF
Drummond, HA
Tarr, DE
McCray, PB
Stokes, JB
Welsh, MJ
Williamson, RA
机构
[1] Univ Iowa, Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA
[2] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA
[3] Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA
[4] Univ Iowa, Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA
[5] Univ Iowa, Coll Med, Dept Pediat, Iowa City, IA 52242 USA
[6] Vet Affairs Med Ctr, Iowa City, IA 52242 USA
关键词
D O I
10.1073/pnas.96.4.1727
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The epithelial Na+ channel (ENaC) is composed of three homologous subunits: alpha, beta and gamma. We used gene targeting to disrupt the beta subunit gene of ENaC in mice. The beta ENaC-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 alpha ENaC-deficient mice, which die because of defective lung liquid clearance, neonatal beta ENaC 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 beta subunit is required for ENaC function in the renal collecting duct, but, in contrast to the alpha subunit, the beta subunit is not required for the transition from a liquid-filled to an air-filled lung. The phenotype of the beta ENaC-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.
引用
收藏
页码:1727 / 1731
页数:5
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