The gene encoding mouse Muc19: cDNA, genomic organization and relationship to Smgc

Abstract

We previously demonstrated expression of full-length transcripts for sublingual mucin apoprotein, Muc19, of approximately 24 kb (Fallon MA, Latchney LR, Hand AR, Johar A, Denny PA, Georgel PT, Denny PC, and Culp DJ. Physiol Genomics 14: 95-106, 2003). We now describe the complete sequence and genomic organization of the apomucin encoded by 43 exons. Southern analyses indicate a central exon of approximately 18 kb containing 36 tandem repeats, each encoding 163 residues rich in serine and threonine. Full-length transcripts are an estimated 22,795 bp in length that span 106 kb of genomic DNA. The transcriptional start site is 24 bp downstream of a TATA box and 42 bp upstream of the conceptual translational start codon. The putative apoprotein has an estimated mass of 693.4 kDa and contains 7,524 amino acids (80% serine, threonine, glycine, alanine, and proline). We present a model for rat Muc19 transcripts and compare the conceptually translated Muc19 proteins for mouse, rat, pig, and the 3' end of human Muc19. Conserved among these apoproteins are a signal peptide, a large tandem repeat region, von Willebrand factor type C and D domains, a trypsin inhibitor-like Cys-rich domain, and a COOH-terminal cystine knot-like domain. Southern blot analyses indicate transcripts for Muc19 and Smgc (submandibular gland protein C) are splice variants of a larger gene, Muc19/Smgc. Comparative Northern analyses between the major salivary glands demonstrate highly selective Muc19 expression in neonatal and adult sublingual glands, whereas Smgc is expressed in neonatal submandibular and sublingual glands. Regulation of Muc19/Smgc gene expression is discussed with respect to alternative splicing and mucous cell cytodifferentiation.

Tissue Distribution of Murine Muc19/Smgc Gene Products

“…Although this antiserum was demonstrated previously to react with mucous cells and with high-molecular-mass glycoproteins from sublingual glands of mice (Culp et al 2004; Das et al Figure 2 Testing the specificity against gel-forming mucins of antiserum raised against purified rat Muc19. Homogenates from select mouse tissues that express Muc19 and/or other gel-forming mucins were subjected to SDS-PAGE (3-8% gradient gels).…”

“…In the oral cavity, gel-forming mucins are secreted by the mucous cell phenotype found within mucous glands such as sublingual glands and multiple minor salivary glands. We use rodent sublingual glands as a model system to investigate mucous cell biology (Culp et al 1996;Luo et al 2001) and identified the gel-forming mucin, Muc19, as a secretory product of murine sublingual mucous cells (Fallon et al 2003;Culp et al 2004). Muc19 is a product of the gene Muc19/Smgc that contains 60 exons and spans ?105 kb of genomic sequence.…”

Cloning and Characterization of Human MUC19 Gene

“…The sequence of this protein perfectly matches mouse Muc19. Soon after, mouse Muc19 was completely sequenced and shown to have a cDNA length of 22,795 bp encoded by a total of 43 exons and spanning 106 kb of genomic DNA (12). It has a gel-forming mucin structure signal peptide, a large central exon with tandem repeats, VWC, VWD, and Cterminal CT domains.…”

“…It has a gel-forming mucin structure signal peptide, a large central exon with tandem repeats, VWC, VWD, and Cterminal CT domains. Interestingly, the mouse Muc19 locus contains an additional transcript, submandibular gland protein C (Smgc) (12). Smgc is a major secretory product, and a marker of the type I (terminal tubule) cells of the neonatal rat and mouse submandibular gland, but its expression in the adult is present only in some intercalated duct cells (13).…”

“…It contains 18 exons. The first exon overlaps with Muc19, and the rest of the sequences are located in intron 1 of Muc19 (12,13).…”