MUCLIN expression in the cystic fibrosis transmembrane conductance regulator knockout mouse.

BACKGROUND & AIMS: Cystic fibrosis is characterized by increased secretion of glycoconjugates with altered carbohydrate composition, but no specific gene products that show these changes have been identified. The aim of this study was to use a recently described sulfated mucin-like glycoprotein (MUCLIN: formerly called gp300) as a model glycoconjugate to study such changes in the gastrointestinal system in the cystic fibrosis transmembrane conductance regulator (CFTR) knockout mouse (cftrm1Unc).
METHODS: Western and Northern blots were used to determine the tissue levels of MUCLIN and its messenger RNA (mRNA) in normal and CFTR knockout mice. Immunocytochemistry was used to determine the localization of MUCLIN.
RESULTS: MUCLIN is expressed in the normal mouse intestinal tract, pancreas, and gallbladder. In CFTR knockout mice, MUCLIN shows increased expression at both mRNA and protein levels in pancreas and duodenum, but not in the gallbladder. In the duodenum, MUCLIN was localized intracellularly in crypt enterocytes and on the luminal surface, and luminal surface labeling was dramatically increased in the CFTR knockout mouse. In the CFTR knockout mouse duodenum and gallbladder, MUCLIN showed retarded electrophoretic migration indicating altered posttranslational processing.
CONCLUSIONS: MUCLIN shows increased expression and possibly altered posttranslational processing in the CFTR knockout mouse and will serve as a good model for understanding changes in the composition of mucous secretions in patients with this disease.