Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis.
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.
Clarke
L L
LL
Department of Medicine, University of North Carolina, Chapel Hill 27514.
Grubb
B R
BR
Gabriel
S E
SE
Smithies
O
O
Koller
B H
BH
Boucher
R C
RC
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009297:Nasal Mucosa / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
D002712:Chlorides; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000584:Amiloride; D000242:Cyclic AMP