A Novel Mouse β-Defensin, mBD-6, Predominantly Expressed in Skeletal Muscle

Abstract

Defensins comprise a family of cationic antimicrobial peptides that is characterized by the conserved 6 cysteine residues. They are expressed in the epithelial cells of various organs and are identified as key elements in the host defense system at the mucosal surface. We isolated a novel mouse ␤-defensin gene from the bacterial artificial chromosome DNA containing the mouse ␤-defensin-3 gene. The full-length cDNA was cloned from skeletal muscle cDNA and called mouse ␤-defensin-6 (mBD-6). The predicted peptide conserved the 6-cysteine motif and had 59% amino acid sequence identity with mouse ␤-defensin-3 and 59% identity with mouse ␤-defensin-4. We demonstrated the expression of mBD-6 in skeletal muscle in addition to the esophagus, tongue, and trachea. In animal models of endotoxemia, mBD-6 expression was also induced in the lung. mBD-6 showed potent antimicrobial activity against Escherichia coli and would play an important role in host defense in the esophagus, airways, and skeletal muscle. mBD-6 is the first reported ␤-defensin predominantly expressed in skeletal muscle. This unique tissue specificity suggests some novel physiological roles of this peptide family.

Discovery of five conserved β-defensin gene clusters using a computational search strategy

“…Similar approaches were used to query the Celera mouse genome assembly (www.celera.com). The initial queries for the search used the amino acid sequences for the known human defensins (DEFB1, DEFB2, DEFB3, and DEFB4) (3-7) and two HE2͞EP2 sequences (8,9) and the known mouse ␤-defensins (Defb1, Defb2, Defb3, Defb4, Defb5, and Defb6) (10)(11)(12)(13)(14) and GenBank (accession no. AF318068).…”

“…The first exon includes the 5Ј untranslated region and encodes the leader domain of the preproprotein; the second exon encodes the mature peptide with the six-cysteine domain. As this project began, five human ␤-defensin genes (3-9) and six mouse ␤-defensin genes (10)(11)(12)(13)(14) were reported or submitted to GenBank (accession no. AF318068).…”

Identification of Multiple Novel Epididymis-Specific β-Defensin Isoforms in Humans and Mice

“…We compared the potency of mBD-12 with mBD-6 and HNP-1 synthetic peptide, whose data had been previously reported (20). mBD-12 bactericidal activity was significantly more potent than HNP-1 at the concentration of 20 g/ml (Student's t test, p Ͻ 0.01) (Fig.…”

“…hBD-1, hBD-2, and hBD-3 showed the widespread distribution in various organs like urogenital tissues, skin, respiratory tracts, intestinal tracts, testis, and placenta (22)(23)(24)(25)(26). Although the tissue distribution of mBD-5, mBD-7, mBD-8, mBD-9, mBD-11, mBD-13, and mBD-35 have not been evaluated in mice, the other known mBD isoforms also show the expression in multiple tissues, such as kidney, esophagus, tongue, trachea, and skeletal muscle (15)(16)(17)(18)(19)(20).…”

“…All hBDs show potent antimicrobial activity, especially against Gram-negative bacteria, whereas the function of HE2␤1 had not been confirmed (5)(6)(7)(12)(13)(14). In mice, mouse ␤-defensin (mBD)-1, -2, -3, -4, -5, -6, -7, -8, -9, -11, -13, and -35 have been identified at the National Center for Biotechnology Information (NCBI) gene bank, although the characteristics of mBD-5, mBD-9, mBD-11, mBD-13, and mBD-35 have not been published (15)(16)(17)(18)(19)(20)(21). mBD-1 and mBD-3 are regarded as mouse homologs of hBD-1 and hBD-2, respectively, and also showed antimicrobial activity (16,18).…”