Murine CFTR channel and its role in regulatory volume decrease of small intestine crypts

Cystic fibrosis (CF) is caused by mutations in the secretory Cl- channel CF TR (cystic fibrosis transmembrane conductance regulator). Variation in the severity of disease has been attributed to mutations in the CFTR gene that cause different degrees of dysfunction of the CFTR Cl- channel. However, st udies of mouse models of CF indicate that the severity of intestinal pathol ogy is not correlated with activity of the CFTR chloride channel. This obse rvation suggests that other 'environmental' factors might be important in d etermining the severity of disease. In this respect, we have identified and characterised an additional cellular defect in intestinal epithelial cells of CF mice, the inability of these cells to regulate their volume after hy potonic challenge. Here, we review the function of murine CFTR as both a Cl - channel and as a regulator of volume-dependent homeostatic cell mechanism s. Copyright (C) 2000 S. Karger AG Basel.