Cystic fibrosis is caused by mutations in CFTR, a gene that encodes a sodium/chloride transporter that is expressed in multiple tissues. This protein regulates the composition of sweat, mucus, and digestive fluids and loss of the protein causes injury to the lungs, pancreas, liver, and intestine. Approximately 15% of babies with cystic fibrosis (CF) are born with an obstruction of the small intestine known as meconium ileus, frequently the first sign of CF. Unlike in humans, meconium ileus occurs in 100% of newborn CF pigs. David Stoltz and colleagues found that transgenic expression of CFTR cDNA in the intestine of CF pigs alleviated meconium ileus; over time, the pigs still exhibited other manifestations of CF, including liver and lung disease, reduced weight gain, and pancreatic destruction. These findings provide insight into the pathophysiology of CF. The accompanying image shows CFTR expression (green) in the ileus of wild type pigs, pigs lacking intestinal CFTR, and pigs expressing recombinant CFTR.
Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people with CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas meconium ileus occurs in 15% of babies with CF, the penetrance is 100% in newborn CF pigs. We hypothesized that transgenic expression of porcine CF transmembrane conductance regulator (
David A. Stoltz, Tatiana Rokhlina, Sarah E. Ernst, Alejandro A. Pezzulo, Lynda S. Ostedgaard, Philip H. Karp, Melissa S. Samuel, Leah R. Reznikov, Michael V. Rector, Nicholas D. Gansemer, Drake C. Bouzek, Mahmoud H. Abou Alaiwa, Mark J. Hoegger, Paula S. Ludwig, Peter J. Taft, Tanner J. Wallen, Christine Wohlford-Lenane, James D. McMenimen, Jeng-Haur Chen, Katrina L. Bogan, Ryan J. Adam, Emma E. Hornick, George A. Nelson IV, Eric A. Hoffman, Eugene H. Chang, Joseph Zabner, Paul B. McCray Jr., Randall S. Prather, David K. Meyerholz, Michael J. Welsh