Genomic organization of MUC4 mucin gene. Towards the characterization of splice variants

The human MUC4 gene encodes a large membrane-associated mucin, characterized by a mucin tandem repeat domain and a growth factor-like transmembrane domain. In addition to the originally published sequence (sv0-MUC4), several MUC4 cDNA sequences (called sv1-MUC4 to sv21-MUC4, MUC4/X, MUC4/Y) from various tissues and cell lines have been recently described. They differ from sv0-MUC4 by deletions and/or insertions located in the 3' region or, for two of them, by deletion of the central repetitive domain. To establish the nature of the mechanisms responsible for the diversity of MUC4 transcripts, the genomic structure of the 3' region of the human MUC4 gene was determined. Our results show that it spans approximately 30.8 kb of genomic DNA and is composed of 24 exons, including one alternative exon which was exclusively reported for sv1-MUC4. Moreover, we have shown that the different MUC4 transcripts are generated by several mechanisms, including the alternative use of cassette exons, exon skipping or use of cryptic splice donor/acceptor sites.