The ENaC-overexpressing mouse as a model of cystic fibrosis lung disease

Zhe Zhou, Julia Duerr, Bjarki Johannesson, Susanne C. Schubert, Diana Treis, Maria Harm, Simon Y. Graeber, Alexander Dalpke, Carsten Schultz, Marcus A. Mall

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Chronic lung disease remains the major cause of morbidity and mortality of cystic fibrosis (CF) patients. Cftr mutant mice developed severe intestinal obstruction, but did not exhibit the characteristic CF ion transport defects (i.e. deficient cAMP-dependent Cl- secretion and increased Na+ absorption) in the lower airways, and failed to develop CF-like lung disease. These observations led to the generation of transgenic mice with airway-specific overexpression of the epithelial Na+ channel (ENaC) as an alternative approach to mimic CF ion transport pathophysiology in the lung. Studies of the phenotype of βENaC-transgenic mice demonstrated that increased airway Na+ absorption causes airway surface liquid (ASL) depletion, reduced mucus transport and a spontaneous CF-like lung disease with airway mucus obstruction and chronic airway inflammation. Here, we summarize approaches that can be applied for studies of the complex in vivo pathogenesis and preclinical evaluation of novel therapeutic strategies in this model of CF lung disease.

Original languageEnglish (US)
Pages (from-to)S172-S182
JournalJournal of Cystic Fibrosis
Volume10
Issue numberSUPPL. 2
DOIs
StatePublished - Jul 1 2011

Keywords

  • Airway inflammation
  • Airway surface liquid
  • Cystic fibrosis
  • ENaC
  • Mouse model
  • Mucus obstruction

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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    Zhou, Z., Duerr, J., Johannesson, B., Schubert, S. C., Treis, D., Harm, M., Graeber, S. Y., Dalpke, A., Schultz, C., & Mall, M. A. (2011). The ENaC-overexpressing mouse as a model of cystic fibrosis lung disease. Journal of Cystic Fibrosis, 10(SUPPL. 2), S172-S182. https://doi.org/10.1016/S1569-1993(11)60021-0