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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 sv21MUC4, MUC4/X, MUC4/Y) from various tissues and cell lines have been recently described. They differ from sv0MUC4 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. | Eur. J. Biochem. 269 3637-3644 2002 FEBS 2002 doi 10.1046 j.1432-1033.2002.03032.x Genomic organization of MUC4 mucin gene Towards the characterization of splice variants Fabienne Escande1 2 3 Laurent Lemaitre1 Nicolas Moniaux4 Surinder K. Batra4 Jean-Pierre Aubert1 2 and Marie-Pierre Buisine1 2 3 1INSERM Unite 560 Lille France 2Laboratoire de Biochimie et Biologie Moleculaire Hopital C. Huriez Centre Hospitalier Regional et Universitaire Lille France 3Faculte de Medecine Henri Warembourg Lille France 4Departement of Biochemistry and Molecular Biology the Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical Center Omaha USA 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 MUC4ỊX MUC4ỊY 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. Keywords MUC4 mucin membrane-associated alternative splicing. Human mucins constitute a complex family of membranebound or secreted O-glycoproteins produced by epithelial cells. They contain a high percentage of threonine and serine residues carrying O-linked glycan chains and .
