title: Airway hyperresponsiveness in FVB/N delta F508 cystic fibrosis transmembrane conductance regulator mice.
abstract: BACKGROUND
  Airway hyperresponsiveness is a feature of clinical CF lung disease. In this study, we investigated whether the FVB/N ΔF508 CFTR mouse model has altered airway mechanics.
  
  
  METHODS
  Mechanics were measured in 12-14week old FVB/N Cftr(tm1Eur) (ΔF508) mice and wildtype littermates using the FlexiVent small animal ventilator. Lung disease was assayed by immunohistochemistry, histology and bronchoalveolar lavage analysis.
  
  
  RESULTS
  Cftr(tm1Eur) mice presented with increased airway resistance, compared to wildtype littermates, in response to methacholine challenge. No differences in bronchoalveolar cell number or differential, or in tissue lymphocyte, goblet cell or smooth muscle actin levels were evident in mice grouped by Cftr genotype. The bronchoalveolar lavage of Cftr(tm1Eur) mice included significantly increased levels of interleukin 12(p40) and CXCL1 compared to controls.
  
  
  CONCLUSIONS
  We conclude that the pulmonary phenotype of Cftr(tm1Eur) mice includes airway hyperresponsiveness in the absence of overt lung inflammation or airway remodeling.
authors.affiliation: Department of Human Genetics, McGill University, 3626 St. Urbain, Montreal, Qc H2X 2P2, Canada; Department of Medicine, McGill University, 3626 St. Urbain, Montreal, Qc H2X 2P2, Canada; The Meakins-Christie Laboratories, McGill University, 3626 St. Urbain, Montreal, Qc H2X 2P2, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Bazett
authors.affiliation: Department of Human Genetics, McGill University, 3626 St. Urbain, Montreal, Qc H2X 2P2, Canada; Department of Medicine, McGill University, 3626 St. Urbain, Montreal, Qc H2X 2P2, Canada; The Meakins-Christie Laboratories, McGill University, 3626 St. Urbain, Montreal, Qc H2X 2P2, Canada. Electronic address: christina.haston@mcgill.ca.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Haston
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005838:Genotype; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D016207:Cytokines; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA
keywords: Airway hyperresponsiveness; Cftr; Lung; Murine models