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A novel mouse beta-defensin, mBD-6, predominantly expressed in skeletal muscle
Y Yamaguchi1, S Fukuhara, T Nagase
1Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
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 beta-defensin gene from the bacterial artificial chromosome DNA containing the mouse beta-defensin-3 gene. The full-length cDNA was cloned from skeletal muscle cDNA and called mouse beta-defensin-6 (mBD-6). The predicted peptide conserved the 6-cysteine motif and had 59% amino acid sequence identity with mouse beta-defensin-3 and 59% identity with mouse beta-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 beta-defensin predominantly expressed in skeletal muscle. This unique tissue specificity suggests some novel physiological roles of this peptide family.
Insights
Researchers discovered a novel mouse beta-defensin-6 (mBD-6) peptide, primarily expressed in skeletal muscle. This defensin exhibits potent antimicrobial activity, suggesting new roles in host defense beyond mucosal surfaces.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Defensins are cationic antimicrobial peptides crucial for host defense, particularly at mucosal surfaces.
- They are characterized by a conserved motif of six cysteine residues.
- Epithelial cells express defensins in various organs.
Purpose of the Study:
- To isolate and characterize a novel mouse beta-defensin gene.
- To determine the expression pattern and antimicrobial activity of the newly identified defensin.
- To investigate potential novel physiological roles of beta-defensins in skeletal muscle.
Main Methods:
- Isolation of a novel mouse beta-defensin gene from bacterial artificial chromosome DNA.
- Cloning of the full-length cDNA for mouse beta-defensin-6 (mBD-6) from skeletal muscle cDNA.
- Analysis of amino acid sequence identity with known beta-defensins (mBD-3, mBD-4).
- Demonstration of mBD-6 expression in various tissues (skeletal muscle, esophagus, tongue, trachea) and induction in the lung during endotoxemia.
- Assessment of antimicrobial activity against Escherichia coli.
Main Results:
- A novel mouse beta-defensin, mBD-6, was identified and cloned.
- mBD-6 shares 59% amino acid identity with mBD-3 and mBD-4 and conserves the 6-cysteine motif.
- mBD-6 is predominantly expressed in skeletal muscle, with additional expression in the esophagus, tongue, and trachea.
- Expression of mBD-6 was induced in the lung in animal models of endotoxemia.
- mBD-6 demonstrated potent antimicrobial activity against Escherichia coli.
Conclusions:
- Mouse beta-defensin-6 (mBD-6) is a novel beta-defensin primarily expressed in skeletal muscle.
- mBD-6 possesses significant antimicrobial activity against Escherichia coli.
- The unique tissue distribution suggests novel roles for beta-defensins in host defense, particularly in skeletal muscle and airways.