MUCLIN EXPRESSION IN THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR KNOCKOUT MOUSE

Background & Aims: Cystic fibrosis is characterized by increased secre tion of glycoconjugates with altered carbohydrate composition, but no specific gene products that show these changes have been identified, T he aim of this study was to use a recently described sulfated mucin-li ke glycoprotein (MUCLIN; formerly called gp300) as a model glycoconjug ate to study such changes in the gastrointestinal system in the cystic fibrosis transmembrane conductance regulator (CFTR) knockout mouse (c ftr(m1Unc)), Methods: Western and Northern blots were used to determin e the tissue levels of MUCLIN and its messenger RNA (mRNA) in normal a nd CFTR knockout mice, Immunocytochemistry was used to determine the l ocalization of MUCLIN, Results: MUCLIN is expressed in the normal mous e intestinal tract, pancreas, and gallbladder, In CFTR knockout mice, MUCLIN shows increased expression at both mRNA and protein levels in p ancreas and duodenum, but not in the gallbladder, In the duodenum, MUC LIN was localized intracellularly in crypt enterocytes and on the lumi nal surface, and luminal surface labeling was dramatically increased i n the CFTR knockout mouse, In the CFTR knockout mouse duodenum and gal lbladder, MUCLIN showed retarded electrophoretic migration indicating altered posttranslational processing, Conclusions: MUCLIN shows increa sed expression and possibly altered posttranslational processing in th e CFTR knockout mouse and will serve as a good model for understanding changes in the composition of mucous secretions in patients with this disease.