Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs

One component of host defense at mucosal surfaces is epithelium-derived pep tides with antimicrobial activity called defensins. We describe in this rep ort the isolation and characterization of a murine homologue of human beta- defensin 2 (hBD-2) called mouse beta-defensin 3 (mBD-3). The predicted amin o acid sequence shows the hallmark features of other known epithelial defen sins, including the ordered array of six cysteine residues. Analysis of a g enomic clone of mBD-3 revealed two exons separated by a 1.7-kb intron. The mBD-3 gene is localized at the proximal portion of chromosome 8, the site w here genes for mouse alpha- and beta-defensins are found. Under basal condi tion, mBD-3 transcripts were detected at low levels in epithelial cells of surface organs, such as the intestine and lung. After instillation of Pseud omonas aeruginosa PAO1 into mouse airways, mBD-3-specific mRNA was upregula ted significantly not only in large airways but also in the small bowel and liver. Recombinant mBD-3 peptide, produced from a baculovirus expression s ystem, showed antimicrobial activity against P. aeruginosa PAO1 (MIC of 8 m u g/ml) and Escherichia coli D31 (MIC of 16 mu g/ml) in a salt dependent ma nner. This study demonstrates that a murine homologue of hBD-2 is present i n the respiratory system and other mucosal surfaces. These similarities bet ween murine and human host defense apparatus provide further impetus to eva luate the mouse as a model for studying the human innate host defense syste m.