A novel murine β-defensin expressed in tongue, esophagus, and trachea*

Abstract

β-Defensins are broad spectrum antimicrobial peptides expressed at epithelial surfaces. Two human β-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 β-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 α-defensins (cryptdins) -3 and -17, consistent with a gene cluster. Our genomic cloning and mapping data suggest that there is a large β-defensin gene family in mice. Identification of murine β-defensins provides an opportunity to understand further the role of these peptides in host defense through animal model studies and the generation of β-defensin-deficient animals by gene targeting.