title: The ENaC-overexpressing mouse as a model of cystic fibrosis lung disease.
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.
authors.affiliation: Division of Pediatric Pulmonology & Allergy and Cystic Fibrosis Center, Department of Pediatrics III, University of Heidelberg, Heidelberg, Germany.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.forename: Julia
authors.initials: J
authors.lastname: Duerr
authors.forename: Bjarki
authors.initials: B
authors.lastname: Johannesson
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Schubert
authors.forename: Diana
authors.initials: D
authors.lastname: Treis
authors.forename: Maria
authors.initials: M
authors.lastname: Harm
authors.forename: Simon Y
authors.initials: SY
authors.lastname: Graeber
authors.forename: Alexander
authors.initials: A
authors.lastname: Dalpke
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Mall
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D053503:Epithelial Sodium Channels / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D053503:Epithelial Sodium Channels; C507049:Scnn1b protein, mouse