LUNG-DISEASE IN MICE WITH CYSTIC-FIBROSIS

The leading cause of mortality and morbidity in humans with cystic fib rosis is lung disease, Advances in our understanding of the pathogenes is of the lung disease of cystic fibrosis, as well as development of i nnovative 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, t o 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 lun g disease include failure of effective mucociliary transport, postbron chiolar over inflation of alveoli and parenchymal interstitial thicken ing, with evidence of fibrosis and inflammatory cell recruitment, We s peculate that the basis for development of lung disease in the congeni c CFTR-knockout mice is their observed lack of a non-CFTR chloride cha nnel normally found in CFTR-knockout mice of mixed genetic background.