Development of Conditionally Immortalized Epithelial Cell Lines from CF and Non-CF Mice

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are responsible for cystic fibrosis (CF) (1 ) and the primary defect in CF is the loss of cAMP-regulated anion conductance in the apical plasma membrane of epithelial cells in affected tissues (2 ,3 ). Primary culture of CF epithelial cells and immortalized cell lines derived from CF patients have been particularly useful for studies of cystic fibrosis and CFTR (4 -9 ). A wide spectrum of phenotypic abnormalities associated with mutant CFTR has been described; however, it is unclear how many of these alterations are related to loss of Cl™ channel function (10 ). Most of the studies of CFTR function have been performed using airway and colon carcinoma (T84) cells or heterologous expression systems (4 -9 ). Epithelial cells from other tissues affected by cystic fibrosis have received relatively little attention, primarily due to the lack of access to appropriate human material. The development of the CF mouse has expanded the number of epithelial cell types available for study (11 ,12 ).