Proliferation, not apoptosis, alters epithelial cell migration in small intestine of CFTR null mice

Expression of a mutated cystic fibrosis transmembrane conductance regulator (CFTR) has been shown to enhance proliferation within CF airways, and cell s expressing a mutated CFTR have been shown to be less susceptible to apopt osis. Because the CFTR is expressed in the epithelial cells lining the gast rointestinal tract and all CF mouse models are characterized by gastrointes tinal obstruction, we hypothesized that CFTR null mice would have increased epithelial cell proliferation and reduced apoptosis within the small intes tine. The rate of intestinal epithelial cell migration from crypt to villus was increased in CFTR null mice relative to mice expressing the wild-type CFTR. This difference in migration could be explained by an increase in epi thelial cell proliferation but not by a difference in apoptosis within the crypts of Lieberkuhn. In addition, using two independent sets of CF cell li nes, we found that epithelial cell susceptibility to apoptosis was unrelate d to the presence of a functional CFTR. Thus increased proliferation but no t alterations in apoptosis within epithelial cells might contribute to the pathophysiology of CF.