title: Lung disease in mice with cystic fibrosis.
abstract: The leading cause of mortality and morbidity in humans with cystic fibrosis is lung disease. Advances in our understanding of the pathogenesis of the lung disease of cystic fibrosis, as well as development of innovative therapeutic interventions, have been compromised by the lack of a natural animal model. The utility of the CFTR-knockout mouse in studying the pathogenesis of cystic fibrosis has been limited because of their failure, despite the presence of severe intestinal disease, to develop lung disease. Herein, we describe the phenotype of an inbred congenic strain of CFTR-knockout mouse that develops spontaneous and progressive lung disease of early onset. The major features of the lung disease include failure of effective mucociliary transport, postbronchiolar over inflation of alveoli and parenchymal interstitial thickening, with evidence of fibrosis and inflammatory cell recruitment. We speculate that the basis for development of lung disease in the congenic CFTR-knockout mice is their observed lack of a non-CFTR chloride channel normally found in CFTR-knockout mice of mixed genetic background.
authors.affiliation: Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Kent
authors.forename: R
authors.initials: R
authors.lastname: Iles
authors.forename: C E
authors.initials: CE
authors.lastname: Bear
authors.forename: L J
authors.initials: LJ
authors.lastname: Huan
authors.forename: U
authors.initials: U
authors.lastname: Griesenbach
authors.forename: C
authors.initials: C
authors.lastname: McKerlie
authors.forename: H
authors.initials: H
authors.lastname: Frndova
authors.forename: C
authors.initials: C
authors.lastname: Ackerley
authors.forename: D
authors.initials: D
authors.lastname: Gosselin
authors.forename: D
authors.initials: D
authors.lastname: Radzioch
authors.forename: H
authors.initials: H
authors.lastname: O'Brodovich
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: M
authors.initials: M
authors.lastname: Buchwald
authors.forename: A K
authors.initials: AK
authors.lastname: Tanswell
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000473:pathology* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004594:Electrophysiology; D005260:Female; D008168:Lung / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000648:ultrastructure; D012129:Respiratory Function Tests; D012720:Severity of Illness Index
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator