TAILIEUCHUNG - Báo cáo Y học: Cloning, chromosomal localization and characterization of the murine mucin gene orthologous to human MUC4

We report here the full coding sequence of a novel mouse putative membrane-associated mucin containing three extracellular EGF-like motifs and a mucin-like domain consisting of at least 20 tandem repeats of 124–126 amino acids. Screening a cosmid and a BAC libraries allowed to isolate several genomic clones. Genomic and cDNA sequence comparisons showed that the gene consists of 25 exons and 24 introns covering a genomic region of 52 kb. The first intron is 16 kb in length and is followed by an unusually large exon ( kb) encoding Ser/Thr-rich tandemly repeated sequences | Eur. J. Biochem. 269 3150-3159 2002 FEBS 2002 doi Cloning chromosomal localization and characterization of the murine mucin gene orthologous to human MUC4 Jean-Luc Desseyn Isabelle Clavereau and Anne Laine Unite 560 INSERM Place de Verdun Lille France We report here the full coding sequence of a novel mouse putative membrane-associated mucin containing three extracellular EGF-like motifs and a mucin-like domain consisting of at least 20 tandem repeats of 124-126 amino acids. Screening a cosmid and a BAC libraries allowed to isolate several genomic clones. Genomic and cDNA sequence comparisons showed that the gene consists of 25 exons and 24 introns covering a genomic region of w 52 kb. The first intron is w 16 kb in length and is followed by an unusually large exon w kb encoding Ser Thr-rich tandemly repeated sequences. Radiation hybrid mapping localized this new gene to a mouse region of chromosome 16 which is the orthologous region of human chromosome 3q29 encompassing the large membrane-anchored mucin MUC4. Contigs analysis of the Human Genome Project did not reveal any other mucin on chromosome 3q29 and interestingly our analysis allowed the determination of the genomic organization of the human MUC4 and showed that its exon intron structure is identical to that of the mouse gene we cloned. Furthermore the human MUC4 shares considerable homologies with the mouse gene. Based on these data we concluded that we isolated the mouse ortholog of MUC4 we propose as Muc4. Expression studies showed that Muc4 is ubiquitous like SMC and MUC4 with highest levels of expression in trachea and intestinal tract. Keywords MUC4 SMC expression large exon tandem repeat. Epithelial mucins are high molecular mass glycoproteins synthesized by secretory epithelia. All mucins have a large domain composed of tandemly repeated sequences rich in serine and threonine residues that carry O-linked oligosaccharides. Epithelial mucins are usually subdivided

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