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Science 21 August 1992:
Vol. 257. no. 5073, pp. 1125 - 1128
DOI: 10.1126/science.257.5073.1125
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Articles

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

Lane L. Clarke 1, Barbara R. Grubb 1, Sherif E. Gabriel 1, Oliver Smithies 2, Beverly H. Koller 1, and Richard C. Boucher 1

1 Division of Pulmonary Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC 27514
2 Department of Medicine, University of North Carolina, Chapel Hill, NC 27514

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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Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland.
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Desensitization of P2Y2 receptor-activated transepithelial anion secretion.
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A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion.
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Pathophysiology of Gene-Targeted Mouse Models for Cystic Fibrosis.
B. R. GRUBB and R. C. BOUCHER (1999)
Physiol Rev 79, 193-214
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Molecular and Functional Characterization of a Calcium-sensitive Chloride Channel from Mouse Lung.
R. Gandhi, R. C. Elble, A. D. Gruber, K. D. Schreur, H.-L. Ji, C. M. Fuller, and B. U. Pauli (1998)
J. Biol. Chem. 273, 32096-32101
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Effect of Host Modification and Age on Airway Epithelial Gene Transfer Mediated by a Murine Leukemia Virus-Derived Vector.
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J. Virol. 72, 8861-8872
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Enamel Mineral Composition of Normal and Cystic Fibrosis Transgenic Mice.
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Advances in Dental Research 10, 270-275
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Journal of Dental Research 75, 966-973
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Science 266, 1705-1708
   Abstract »    PDF »
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Science 266, 107-109
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Notch1 is essential for postimplantation development in mice..
P J Swiatek, C E Lindsell, F F del Amo, G Weinmaster, and T Gridley (1994)
Genes & Dev. 8, 707-719
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J. Cell Sci. 107, 2439-2448
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Knockout Mice Offer First Animal Model for CF.
M. Barinaga (1992)
Science 257, 1046-1047
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