The duct cell in cystic fibrosis.
The pancreatic duct cell is central to the etiology of cystic fibrosis (CF) and is the site where pathology commences in utero. We have evaluated expression of the cystic fibrosis transmembrane conductance regulator gene (CFTR) through human development and shown it to be expressed from the early mid-trimester, with highest levels in the most distal portion of the developing duct system and in centroacinar cells. The precise cause of pancreatic destruction in CF is thought to be the obstruction of pancreatic ducts with inspissated secretions. We have shown that the MUC6 mucin is a significant component of the material that obstructs the ducts and that the MUC6 gene shows a very similar pattern of expression to that of CFTR in the developing pancreas. These observations provide a starting point for investigating how mutations in CFTR lead to obstruction of the pancreatic ducts in CF.
Harris
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Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital, UK. aharris@molbiol.ox.ac.uk
D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D055272:Mucin-6; D009077:Mucins / Q000235:genetics*; D016296:Mutagenesis; D010183:Pancreatic Ducts / Q000196:embryology* / Q000473:pathology
C505032:CFTR protein, human; C524734:MUC6 protein, human; D055272:Mucin-6; D009077:Mucins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator