Characteristics of rodent intestinal mucin Muc3 and alterations in a mouse model of human cystic fibrosis.
Human mucin MUC3 and rodent Muc3 are widely assumed to represent secretory mucins expressed in columnar and goblet cells of the intestine. Using a 3'-oligonucleotide probe and in situ hybridization, we observed expression of rat Muc3 mostly in columnar cells. Two antibodies specific for COOH-terminal epitopes of Muc3 localized to apical membranes and cytoplasm of columnar cells. An antibody to the tandem repeat (TR) sequence (TTTPDV)3, however, localized to both columnar and goblet cells. On CsCl gradients, Muc3 appeared in both light- and heavy-density fractions. The lighter species was immunoreactive with all three antibodies, whereas the heavier species reacted only with anti-TR antibody. Thus Muc3 is expressed in two forms, a full-length membrane-associated form found in columnar cells (light density) and a carboxyl-truncated soluble form present in goblet cells (heavy density). In a mouse model of human cystic fibrosis, both soluble Muc3 and goblet cell Muc2 were increased in amount and hypersecreted. Thus Muc2 and Muc3 contribute to the excess intestinal luminal mucus of cystic fibrosis mice.
Khatri
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Division of Biochemistry and Structural Biology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
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Forstner
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D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002586:Cesium; D002712:Chlorides; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000473:pathology; D008297:Male; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D008969:Molecular Sequence Data; D055262:Mucin-2; D055263:Mucin-3; D009077:Mucins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013393:Sucrase / Q000378:metabolism; D014018:Tissue Distribution
D002712:Chlorides; D000939:Epitopes; C524625:MUC2 protein, human; C524626:Muc2 protein, mouse; C524628:Muc2 protein, rat; C524641:Muc3 protein, mouse; C524651:Muc3 protein, rat; D055262:Mucin-2; D055263:Mucin-3; D009077:Mucins; D002586:Cesium; D013393:Sucrase; C028019:cesium chloride