Alternative splicing generates a family of putative secreted and membrane-associated MUC4 mucins

The MUC4 mucin gene encodes a putative membrane-anchored mucin with predict ed size of 930 kDa, for its 26.5-kb allele. It is composed of two regions, the 850-kDa mucin-type subunit MUC4 alpha and the 80-kDa membrane-associate d subunit MUC4 beta. In this study, we cloned and characterized unique MUC4 cDNA sequences that differ from the originally published sequence. Eight a lternative splice events located downstream of the central large tandem rep eat array generated eight new, distinct cDNAs. The deduced sequences of the se MUC4 cDNAs (sv1-MUC4 to sv8-MUC4, the full length cDNA being called sv0- MUC4) provided seven distinct variants, five secreted forms and two membran e-associated forms. Furthermore, two other alternative splicing events loca ted on both sides of the tandem repeat array created two variants, MUC4/Y a nd MUC4/X, both lacking the central tandem repeat. Therefore, MUC4 can be e xpressed in three distinct forms, one membrane-bound, one secreted, and one lacking the hallmark feature of mucin, the tandem repeat array. Although n o specific function has yet been discovered for the family of proteins puta tively produced from the unique MUC4 gene, we suspect that the MUC4 protein s may be implicated in the integrity and renewal of the epithelium.