title: Beta-defensin overexpression induces progressive muscle degeneration in mice.
abstract: Defensins comprise a family of cationic antimicrobial peptides characterized by conserved cysteine residues. They are produced in various organs including skeletal muscle and are identified as key elements in the host defense system as potent effectors. At the same time, defensins have potential roles in the regulation of inflammation and, furthermore, can exert cytotoxic effects on several mammalian cells. Here, we developed transgenic mice overexpressing mouse beta-defensin-6 to explore the pathophysiological roles of the defensin family as a novel mediator of inflammatory tissue injury. Unexpectedly, the transgenic mice showed short lifespan, poor growth, and progressive myofiber degeneration with functional muscle impairment, predominant centronucleated myofibers, and elevated serum creatine kinase activity, as seen in human muscular dystrophy. Furthermore, some of the transgenic myofibers showed IkappaBalpha accumulation, which would be related to the myofiber apoptosis of limb-girdle muscular dystrophy type 2A. The present findings may unravel a concealed linkage between the innate immune system and the pathophysiology of degenerative diseases.
authors.affiliation: Dept. of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Takahide
authors.initials: T
authors.lastname: Nagase
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Tomita
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Fukuhara
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Amano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yukie
authors.initials: Y
authors.lastname: Ide
authors.forename: Misao
authors.initials: M
authors.lastname: Suzuki
authors.forename: Shinji
authors.initials: S
authors.lastname: Teramoto
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000375:Aging; D000818:Animals; D023082:Defensins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000378:metabolism; D007738:Kyphosis; D008136:Longevity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics* / Q000378:metabolism*; D015430:Weight Gain
chemical_list: C434952:Defb6 protein, mouse; D023082:Defensins; D051550:I-kappa B Kinase