UNDERSTANDING HOW CYSTIC-FIBROSIS MUTATIONS CAUSE A LOSS OF C1(-) CHANNEL FUNCTION

Defective epithelial Cl secretion is the hallmark of the lethal geneti c disease cystic fibrosis (CF). This abnormality is caused by mutation s irt the cystic fibrosis transmembrane conductance regulator (CFTR), a regulated Cl channel. Since the identification of the single gene en coding CFTR, several hundred disease-causing mutations, associated wit h a wide variety of clinical phenotypes, have been reported. To unders tand the relationship between genotype and clinical phenotype, researc hers have investigated how mutations In CFTR disrupt its function. Her e, we review the recent progress in understanding how CF-associated mu tations in CFTR produce defective Cl- channels, and discuss the implic ations of this knowledge for the development of therapy for CF.