Respiratory distress and perinatal lethality in Nedd4-2-deficient mice.
Respiratory distress and perinatal lethality in Nedd4-2-deficient mice.
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DOI：
10.1038/ncomms1284
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发表时间：
2011
影响因子：
16.6
通讯作者：
Kumar, Sharad
中科院分区：
文献类型：
--
作者：
Boase, Natasha A.;Rychkov, Grigori Y.;Townley, Scott L.;Dinudom, Anuwat;Candi, Eleanora;Voss, Anne K.;Tsoutsman, Tatiana;Semsarian, Chris;Melino, Gerry;Koentgen, Frank;Cook, David I.;Kumar, Sharad
上皮钠通道（ENaC）是许多上皮细胞钠稳态所必需的。ENaC活性是新生动物肺液清除和成人血容量和血压维持所必需的。体外研究表明，泛素连接酶Nedd 4 -2泛素化ENaC以调节其细胞表面表达。在这里，我们表明，敲除小鼠中的Nedd 4 -2导致胚胎肺中ENaC表达和活性增加。ENaC活性的增加可能是Nedd 4 -2−/−动物中胎仔肺液体过早清除的原因，导致肺部充气失败和围产期死亡。一小部分Nedd 4 -2−/−动物存活长达22天，这些动物也表现出ENaC表达增加，并发展出致命的肺部无菌炎症。因此，我们提供了关键的体内证据，Nedd 4 -2是必要的ENaC表达，胎儿和出生后的肺功能和动物生存的正确调节。体外研究表明，泛素连接酶Nedd 4 -2调节几种蛋白质，包括上皮钠通道。通过检测Nedd 4 -2缺陷小鼠，作者证明Nedd 4 -2对上皮钠通道调节、胎儿和出生后肺功能以及动物存活至关重要。
The epithelial sodium channel (ENaC) is essential for sodium homoeostasis in many epithelia. ENaC activity is required for lung fluid clearance in newborn animals and for maintenance of blood volume and blood pressure in adults. In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression. Here we show that knockout of Nedd4-2 in mice leads to increased ENaC expression and activity in embryonic lung. This increased ENaC activity is the likely reason for premature fetal lung fluid clearance in Nedd4-2−/− animals, resulting in a failure to inflate lungs and perinatal lethality. A small percentage of Nedd4-2−/− animals survive up to 22 days, and these animals also show increased ENaC expression and develop lethal sterile inflammation of the lung. Thus, we provide critical in vivo evidence that Nedd4-2 is essential for correct regulation of ENaC expression, fetal and postnatal lung function and animal survival. In vitro studies have suggested that the ubiquitin ligase, Nedd4-2, regulates several proteins, including the epithelial sodium channel. Here by examining Nedd4-2-deficient mice, the authors demonstrate that Nedd4-2 is essential for epithelial sodium channel regulation, fetal and postnatal lung function and animal survival.
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影响因子：
4.4
作者：
Kumar, S;Harvey, KF;Jenkins, NA
通讯作者：
Jenkins, NA
影响因子：
4.8
作者：
Konstas, AA;Shearwin-Whyatt, LM;Kumar, S
通讯作者：
Kumar, S
DOI：
10.1164/rccm.200708-1233oc
发表时间：
2008-04-01
影响因子：
24.7
作者：
Mall, Marcus A.;Harkema, Jack R.;Boucher, Richard C.
通讯作者：
Boucher, Richard C.
DOI：
10.1152/ajpgi.1999.276.3.g567
发表时间：
1999-03-01
影响因子：
4.5
作者：
Hummler, E;Horisberger, JD
通讯作者：
Horisberger, JD
DOI：
10.1165/rcmb.2009-0058oc
发表时间：
2010-02-01
影响因子：
6.4
作者：
Conkright, Juliana J.;Apsley, Karen S.;Weaver, Timothy E.
通讯作者：
Weaver, Timothy E.