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). The principal manifestations of CF include increased concentration of Cl- in exocrine gland secretions, pancreatic insufficiency, chronic lung disease, intestinal blockage and malabsorption of fat, and male and female infertility. 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 crypts and reabsorption in the silivary gland ducts, 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. Postmeiotic 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.

Cystic fibrosis transmembrane conductance regulator with a shortened R domain rescues the intestinal phenotype of CFTR −/− mice

“…Consistent with previous reports (32)(33)(34), CFTR localized primarily in the crypts and not the villi of CFTR +/+ mouse intestine (Fig. 5).…”

The distribution and expression of CFTR restricts electrogenic anion secretion to the ileum of the brushtail possum, Trichosurus vulpecula

“…Within the possum ileum, CFTR is expressed in the crypts and base of the villi, with decreasing levels of expression along the villi and little or no expression in the cells at the tips of the villi. This is very similar to the expression pattern for CFTR in the crypt/villous axis of the eutherian small intestine (Ameen et al, 2000b;Strong et al, 1994;Trezise and Buchwald, 1991), although in the possum ileum we did not see any evidence of the CFTR high expresser (CHE) cells that have been reported in rats and humans (Ameen et al, 1995). However, these CHE cells are restricted to the proximal intestine of rats and humans and are absent in other eutherian mammals (Ameen et al, 2000a).…”

“…This is markedly different from the expression of CFTR in the eutherian intestine, where the highest levels of expression occur in the duodenum with decreasing levels of expression in the jejunum and ileum (Ameen et al, 2000b;Strong et al, 1994;Trezise and Buchwald, 1991). Within the possum ileum, CFTR is expressed in the crypts and base of the villi, with decreasing levels of expression along the villi and little or no expression in the cells at the tips of the villi.…”

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

“…Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10]. The expression of CFTR is located in the apical membrane of epithelial cells that line mucous membranes and submucosal glands [11,12]. The tissues most affected by CFTR deficiency include the vas deferens, exocrine pancreas, liver, large intestine, sinuses, and the lower airways.…”