Cystic Fibrosis Remodeled

Science Signaling  30 Sep 2008:
Vol. 1, Issue 39, pp. ec342
DOI: 10.1126/scisignal.139ec342

Cystic fibrosis (CF) is caused by mutational disruption of CFTR, a gene encoding an ion channel required for chloride- and bicarbonate-mediated fluid secretion in epithelia and for salt absorption in many organs. Two decades of intense research on CFTR has not yet translated into new clinical therapies, in part because mice--the traditional animal model for human disease research--do not develop the full spectrum of pathologies seen in human CF. To address this problem, Rogers et al. have inactivated the CFTR gene in pigs, an animal that shares many anatomical and physiological features of humans. Newborn pigs lacking CFTR developed many of the gastrointestinal pathologies seen in infants with CF, including intestinal obstruction and abnormalities of the pancreas, liver, and gallbladder, and their nasal epithelia showed defects in chloride transport. These results, while still preliminary, suggest that the pig model may be a valuable tool for testing new therapies for CF.

C. S. Rogers, D. A. Stoltz, D. K. Meyerholz, L. S. Ostedgaard, T. Rokhlina, P. J. Taft, M. P. Rogan, A. A. Pezzulo, P. H. Karp, O. A. Itani, A. C. Kabel, C. L. Wohlford-Lenane, G. J. Davis, R. A. Hanfland, T. L. Smith, M. Samuel, D. Wax, C. N. Murphy, A. Rieke, K. Whitworth, A. Uc, T. D. Starner, K. A. Brogden, J. Shilyansky, P. B. McCray, Jr., J. Zabner, R. S. Prather, M. J. Welsh, Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 321, 1837-1841 (2008). [Abstract] [Full Text]