Disruption of the β subunit of the epithelial Na+ channel in mice:: Hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype
Disruption of the β subunit of the epithelial Na+ channel in mice:: Hyperkalemia and neonatal death associated with a pseudohypoaldosteronism phenotype
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DOI：
10.1073/pnas.96.4.1727
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发表时间：
1999-02-16
影响因子：
11.1
通讯作者：
Williamson, RA
中科院分区：
文献类型：
--
作者：
McDonald, FJ;Yang, BL;Williamson, RA
上皮性钠离子通道(ENaC)由三个同源亚基组成：α、β和γ。我们使用基因打靶技术在小鼠体内干扰了ENaC的β亚基基因。β-ENaC缺陷小鼠显示出正常的产前发育，但在出生后2天内死亡，很可能是高钾血症。在-/-小鼠中，我们发现尽管有低钠血症，但尿钠浓度升高，而尽管有高钾血症，尿钾浓度却降低。此外，血清醛固酮水平也升高。与因肺液清除缺陷而死亡的α-ENaC缺陷小鼠不同，新生的β-ENaC缺陷小鼠不会死于呼吸衰竭，而且只表现出少量的湿肺重量增加，几乎没有不良的生理后果。结果表明，在体内，肾脏集合管的ENaC功能需要β亚基，但与α亚基相反，从充满液体的肺到充满空气的肺的转变不需要β亚基。β-ENaC缺陷小鼠的表型与人类假性低醛固酮增多症1型相似，可能为研究这种疾病的发病机制和治疗提供了一个有用的模型。
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.