Defective Epithelial Chloride Transport in a Gene-Targeted Mouse Model of Cystic Fibrosis

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Science  21 Aug 1992:
Vol. 257, Issue 5073, pp. 1125-1128
DOI: 10.1126/science.257.5073.1125


The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an adenosine 3', 5'-monophosphate (cyclic AMP)—activated chloride channel. In cystic fibrosis (CF) patients, loss of CFTR function because of a genetic mutation results in defective cyclic AMP—mediated chloride secretion across epithelia. Because of their potential role as an animal model for CF, mice with targeted disruption of the murine CFTR gene [CFTR(-/-)] were tested for abnormalities in epithelial chloride transport. In both freshly excised tissue from the intestine and in cultured epithelia from the proximal airways, the cyclic AMP—activated chloride secretory response was absent in CFTR(-/-) mice as compared to littermate controls. Thus, disruption of the murine CFTR gene results in the chloride transport abnormalities predicted from studies of human CF epithelia.

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