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Published ahead of print on July 25, 2003, doi:10.1165/rcmb.2003-0103OC

Am. J. Respir. Cell Mol. Biol., Volume 30, Number 2, February 2004, 155-165

A more recent version of this article appeared on February 1, 2004
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Submitted on March 26, 2003
Revised on July 23, 2003

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

Yin Chen1, Yu H Zhao1, Tejas B Kalaslavadi1, Edward Hamati1, Keith Nehrke2, Anh D Le3, David K Ann4, and Reen Wu1*

1 Center for Comparative Respiratory Biology and Medicine, University of California at Davis, Davis, CA, USA, 2 Center for Oral Biology, University of Rochester, Rochester, NY, USA, 3 Department of Oral and Maxillofacial Surgery, Drew University of Medicine and Science, Los Angeles, CA, USA, 4 Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA, USA

* To whom correspondence should be addressed. 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. In order 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 EST 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 homologue. We found one vWF C domain (VWC), 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 (vWD) 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 orthologue and Muc19 to the mouse.




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