Pathophysiologic evaluation of the transgenic CFTR "gut-corrected" porcine model of cystic fibrosis

This study evaluated the pulmonary pathophysiology of pigs with transgenic CFTR "gut-corrected" cystic fibrosis (CF). Four sows produced 18 piglets of which 11 were stillborn, with only 2 animals surviving beyond 2 wk. Failure to survive beyond the neonatal period by five piglets was judged to result from metabolic dysfunction related to genetic manipulation for CFTR gut expression or due to cloning artifact. Plasma analysis showed very low plasma proteins, highly elevated liver enzymes, and severe acidosis. All surviving offspring received furosemide for systemic edema. Physiologic evaluation was performed with lung tissues from the two surviving pigs. Both acetylcholine and forskolin induced mucous liquid secretion that was significantly lower in bronchi of pigs with CF than those without CF. The percent of nonvolatile solids in mucus secreted from CF bronchi was elevated following acetylcholine or forskolin treatment. Mucociliary transport in excised tracheas was reduced in the CF tracheas relative to non-CF tracheas. The diameter of tracheas in pigs with CF was less than that of pigs without CF despite their greater body weight. Despite exhibiting severe metabolic dysfunction during the neonatal period, this CF animal model appears to express important characteristics of human CF pulmonary disease.