In vivo cell-specific expression of the cystic fibrosis transmembrane conductance regulator

Abstract

CYSTIC fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR)^1–3. The principal manifestations of CF include increased concentration of Cl⁻ in exocrine gland secretions^4,5, pancreatic insufficiency, chronic lung disease, intestinal blockage and malabsorption of fat^5,6, and male and female infertility⁷. Insight into the function of CFTR can be gained by correlating its cell-specific expression with the physiology of those cells and with CF pathology. Determination of CFTR messenger RNA in rat tissues by in situ hybridization shows that it is specifically expressed in the ductal cells of the pancreas and the salivary glands. In the intestine, decreasing gradients of expression of the CFTR gene are observed on both the crypt–villus and the proximal–distal axes. This expression is consistent with CFTR being responsible for bidirectional Cl⁻ transport, secretion in the intestinal crypts⁸ and reabsorption in the silivary gland ducts⁴, and suggests that in these tissues CFTR functions as a regulated Cl⁻ channel. In the lung, a broad band of hybridization includes the mucosa and submucosa of the bronchi and bronchioles. In the testis, CFTR expression is regulated during the cycle of the seminiferous epithelium. Post-meiotic expression is maximal in the round spermatids of stages VII and VIII, suggesting that CFTR plays a critical role in spermatogenesis and that deficiency of this function contributes to CF male infertility.