Respiratory distress and perinatal lethality in Nedd4-2-deficient mice

Natasha A. Boase, Grigori Y. Rychkov, Scott L. Townley, Anuwat Dinudom, Eleanora Candi, Anne K. Voss, Tatiana Tsoutsman, Chris Semsarian, Gerry Melino, Frank Koentgen, David I. Cook, Sharad Kumar

Research output: Contribution to journalArticle

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Abstract

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.

LanguageEnglish
Article number287
JournalNature communications
Volume2
Issue number1
DOIs
Publication statusPublished - 27 Apr 2011

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Boase, N. A., Rychkov, G. Y., Townley, S. L., Dinudom, A., Candi, E., Voss, A. K., ... Kumar, S. (2011). Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. Nature communications, 2(1), [287]. https://doi.org/10.1038/ncomms1284
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. / Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. In: Nature communications. 2011 ; Vol. 2, No. 1.
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Boase, NA, Rychkov, GY, Townley, SL, Dinudom, A, Candi, E, Voss, AK, Tsoutsman, T, Semsarian, C, Melino, G, Koentgen, F, Cook, DI & Kumar, S 2011, 'Respiratory distress and perinatal lethality in Nedd4-2-deficient mice', Nature communications, vol. 2, no. 1, 287. https://doi.org/10.1038/ncomms1284

Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. / 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.

In: Nature communications, Vol. 2, No. 1, 287, 27.04.2011.

Research output: Contribution to journalArticle

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AU - Cook, David I.

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