Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis.

Clarke LL, Grubb BR, Gabriel SE, Smithies O, Koller BH, Boucher RC:
Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis.
Science 1992 Aug 21;257(5073):1125-8

ABSTRACT
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.