Characteristics of rodent intestinal mucin Muc3 and alterations in a mousemodel 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-termina l 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 appear ed in both light- and heavy-density fractions. The lighter species was immu noreactive with all three antibodies, whereas the heavier species reacted o nly with anti-TR antibody. Thus Muc3 is expressed in two forms, a full-leng th membrane-associated form found in columnar cells (light density) and a c arboxyl-truncated soluble form present in goblet cells (heavy density). In a mouse model of human cystic fibrosis, both soluble Muc3 and goblet cell M uc2 were increased in amount and hypersecreted. Thus Muc2 and Muc3 contribu te to the excess intestinal luminal mucus of cystic fibrosis mice.