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Originally published In Press as doi:10.1074/jbc.M006603200 on August 1, 2000

J. Biol. Chem., Vol. 275, Issue 43, 33314-33320, October 27, 2000
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A Novel Murine beta -Defensin Expressed in Tongue, Esophagus, and Trachea*

Hong Peng JiaDagger , Stephen A. Wowk§, Brian C. SchutteDagger , Sarah K. Lee§, Andrea VivadoDagger , Brian F. Tack||, Charles L. Bevins§, and Paul B. McCray Jr.Dagger **

From the Departments of Dagger  Pediatrics,  Genetics Ph.D. Program, and || Microbiology, University of Iowa College of Medicine, Iowa City, Iowa 52242 and the § Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195

beta -Defensins are broad spectrum antimicrobial peptides expressed at epithelial surfaces. Two human beta -defensins, HBD-1 and HBD-2, have been identified. In the lung, HBD-2 is an inducible product of airway epithelia and may play a role in innate mucosal defenses. We recently characterized rat homologs (RBD-1, RBD-2) of the human genes and used these sequences to identify novel mouse genes. Mouse beta -defensin-4 (MBD-4) was amplified from lung cDNA using polymerase chain reaction primers designed from conserved sequences of RBD-2 and HBD-2. A full-length cDNA was cloned which encodes a putative peptide with the sequence MRIHYLLFTFLLVLLSPLAAFTQIINNPITCMTNGAICWGPCPTAFRQIGNCGHFKVRCCKIR. The peptide shares ~40% identity with HBD-2. MBD-4 mRNA was expressed in the esophagus, tongue, and trachea but not in any of 20 other tissues surveyed. Cloning of the genomic sequence of MBD-4 revealed two nearly (>99%) identical sequences encoding MBD-4 and the presence of numerous additional highly similar genomic sequences. Radiation hybrid mapping localized this gene to a region of chromosome 8 near several other defensins, MBD-2, MBD-3, and alpha -defensins (cryptdins)-3 and -17, consistent with a gene cluster. Our genomic cloning and mapping data suggest that there is a large beta -defensin gene family in mice. Identification of murine beta -defensins provides an opportunity to understand further the role of these peptides in host defense through animal model studies and the generation of beta -defensin-deficient animals by gene targeting.

* This work was supported in part by National Institutes of Health Grants HL-61234-01 (to B. C. S., B. F. T., and P. B. M.) and AI-32234 and AI-32738 (to C. L. B.) and by the Children's Miracle Network Telethon.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF15882, AF287475, and AF288371.

** Recipient of a career investigator award from the American Lung Association. To whom correspondence should be addressed: Dept. of Pediatrics, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Iowa City, IA 52242. Tel.: 319-356-4866; Fax: 319-356-7171; E-mail: paul-mccray@uiowa.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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