Delta F508 CFTR protein expression in tissues from patients with cystic fibrosis.
Kalin, Nanette; ClaaB, Andreas; Sommer, Martin; Puchelle, Edith; Tummler, Burkhard
[Miscellaneous Article] Journal of Clinical Investigation. 103(10):1379-1389, May 1999.

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Heterologous expression of the cystic fibrosis transmembrane conductance regulator (CFTR) provided evidence that the major cystic fibrosis (CF) mutation Delta F508 leads to defective protein folding in the endoplasmic reticulum, which prevents its processing and targeting to the cell surface.In this study, we investigated endogenous CFTR expression in skin biopsies and respiratory and intestinal tissue specimens from Delta F508 homozygous and non-CF patients, using immunohistochemical and immunoblot analyses with a panel of CFTR antibodies. CFTR expression was detected at the luminal surface of reabsorptive sweat ducts and airway submucosal glands, at the apex of ciliated cells in pseudostratified respiratory epithelia and of isolated cells of the villi of duodenum and jejunum, and within intracellular compartments of intestinal goblet cells. In Delta F508 homozygous patients, expression of the mutant protein proved to be tissue specific. Whereas Delta F508 CFTR was undetectable in sweat glands, the expression in the respiratory and intestinal tracts could not be distinguished from the wild-type by signal intensity or localization. The tissue-specific variation of Delta F508 CFTR expression from null to apparently normal amounts indicates that Delta F508 CFTR maturation can be modulated and suggests that determinants other than CFTR mislocalization should play a role in Delta F508 CF respiratory and intestinal disease.

J.Clin. Invest. 103:1379-1389 (1999).

Copyright (C) 1999 The American Society for Clinical Investigation, Inc.