Airway hyperresponsiveness in FVB/N delta F508 cystic fibrosis transmembrane conductance regulator mice

BackgroundAirway 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.MethodsMechanics were measured in 12–14 week 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.ResultsCftr^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.ConclusionWe conclude that the pulmonary phenotype of Cftr^tm1Eur mice includes airway hyperresponsiveness in the absence of overt lung inflammation or airway remodeling.