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

beta -Defensins are broad spectrum antimicrobial peptides expressed at epit helial surfaces. Two human p-defensins, HBD-1 and HBD-2, have been identifi ed, 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 homol ogs (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 c DNA using polymerase chain reaction primers designed from conserved sequenc es of RBD-2 and HBD-2. A full-length cDNA was cloned which encodes a putati ve peptide with the sequence MRIHYLLFTFLLVLLSPLAAFTQIINNPITCMTNGAIC-WGPCPTA FRQIGNCGHFKVRCCKIR . The peptide shares similar to 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 prese nce of numerous additional highly similar genomic sequences. Radiation hybr id mapping localized this gene to a region of chromosome 8 near several oth er defensins, MBD-2, MBD-3, and alpha -defensins (cryptdins)-3 and -17, con sistent with a gene cluster, Our genomic cloning and mapping data suggest t hat there is a large beta -defensin gene family in mice. Identification of murine beta -defensins provides an opportunity to understand further the ro le of these peptides in host defense through animal model studies and the g eneration of beta -defensin-deficient animals by gene targeting.