PT  - JOURNAL ARTICLE
AU  - Clarke, Lane L.
AU  - Grubb, Barbara R.
AU  - Gabriel, Sherif E.
AU  - Smithies, Oliver
AU  - Koller, Beverly H.
AU  - Boucher, Richard C.
TI  - Defective Epithelial Chloride Transport in a Gene-Targeted Mouse Model of Cystic Fibrosis
AID  - 10.1126/science.257.5073.1125
DP  - 1992 Aug 21
TA  - Science
PG  - 1125--1128
VI  - 257
IP  - 5073
4099  - http://science.sciencemag.org/content/257/5073/1125.short
4100  - http://science.sciencemag.org/content/257/5073/1125.full
SO  - Science1992 Aug 21; 257
AB  - 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.