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Published ahead of print on July 25, 2003, doi:10.1165/rcmb.2003-0103OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 155-165, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0103OC

Genome-Wide Search and Identification of a Novel Gel-Forming Mucin MUC19/Muc19 in Glandular Tissues

Yin Chen, Yu Hua Zhao, Tejas Baba Kalaslavadi, Edward Hamati, Keith Nehrke, Anh Dao Le, David K. Ann and Reen Wu

Center for Comparative Respiratory Biology and Medicine and Division of Pulmonary and Critical Care Medicine, University of California, Davis, California; Center for Oral Biology, University of Rochester, Rochester, New York; Department of Oral and Maxillofacial Surgery, Drew University of Medicine and Science, Los Angeles; and Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, California

Address correspondence to: Reen Wu, Ph.D., Center for Comparative Respiratory Biology and Medicine, Surge 1 Annex, Room 1121, University of California at Davis, One Shields Ave., Davis, CA 95616. E-mail: rwu{at}ucdavis.edu

Gel-forming mucins are major contributors to the viscoelastic properties of mucus secretion. Currently, four gel-forming mucin genes have been identified: MUC2, MUC5AC, MUC5B, and MUC6. All these genes have five major cysteine-rich domains (four von Willebrand factor [vWF] C or D domains and one Cystine-knot [CT] domain) as their distinctive features, in contrast to other non–gel-forming type of mucins. The CT domain is believed to be involved in the initial mucin dimer formation and have very succinct relationship between different gel-forming mucins across different species. Because of gene duplication and evolutional modification, it is very likely that other gel-forming mucin genes exist. To search for new gel-forming mucin candidate genes, a "Hidden Markov Model"(HMM) was built from the common features of the CT domains of those gel-forming mucins. By using this model to screen all protein databases as well as the six-frame translated expression sequence tag and translated human genomic databases, we identified a locus located at the peri-centromere region of human chromosome 12 and the corresponding homologous region of mouse chromosome 15. We cloned the 3' end of this gene and its mouse homolog. We found one vWF C domain, one CT domain, and various mucin-like threonine/serine-rich repeats. Phylogenetic analysis indicated the close relationship between this gene and the submaxillary mucin from porcine and bovine. A polydispersed signal was observed on the Northern blot, which indicates very large mRNA size. Further analysis of the upstream genomic sequences generated from human and mouse genome projects revealed three additional vWF D domains and many mucin-like threonine/serine-rich repeats. The expression of this gene is restricted to the mucous cells of various glandular tissues, including sublingual gland, submandibular gland, and submucosal gland of the trachea. Based on the chronological convention, we have given the name MUC19 to the human ortholog and Muc19 to the mouse.

Abbreviations: bovine submaxillary mucins, BSM • Cystine-knot domain, CT • glyceraldehyde-phosphate dehydrogenase, GAPDH • Hidden Markov Model, HMM • expression sequence tag, EST • polymerase chain reaction, PCR • porcine submaxillary mucins, PSM • reverse transcriptase, RT • saline sodium citrate, SSC • von Willebrand factor C domain, VWC • von Willebrand factor D domain, VWD • von Willebrand factor, vWF




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