title: Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice.
abstract: beta-Sarcoglycan, one of the subunits of the sarcoglycan complex, is a transmembranous glycoprotein which associates with dystrophin and is the molecule responsible for beta-sarcoglycanopathy, a Duchenne-like autosomal recessive muscular dystrophy. To develop an animal model of beta-sarcoglycanopathy and to clarify the role of beta-sarcoglycan in the pathogenesis of the muscle degeneration in vivo, we developed beta-sarcoglycan-deficient mice using a gene targeting technique. beta-Sarcoglycan-deficient mice (BSG(-)(/-)mice) exhibited progressive muscular dystrophy with extensive degeneration and regeneration. The BSG(-)(/-)mice also exhibited muscular hypertrophy characteristic of beta-sarcoglycanopathy. Immunohistochemical and immunoblot analyses of BSG(-)(/-)mice demonstrated that deficiency of beta-sarcoglycan also caused loss of all of the other sarcoglycans as well as of sarcospan in the sarcolemma. On the other hand, laminin-alpha2, alpha- and beta-dystroglycan and dystrophin were still present in the sarcolemma. However, the dystrophin-dystroglycan complex in BSG(-)(/-)mice was unstable compared with that in the wild-type mice. Our data suggest that loss of the sarcoglycan complex and sarcospan alone is sufficient to cause muscular dystrophy, that beta-sarcoglycan is an important protein for formation of the sarcoglycan complex associated with sarcospan and that the role of the sarcoglycan complex and sarcospan may be to strengthen the dystrophin axis connecting the basement membrane with the cytoskeleton.
authors.affiliation: Division of Cell Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Araishi
authors.forename: T
authors.initials: T
authors.lastname: Sasaoka
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
authors.forename: H
authors.initials: H
authors.lastname: Hama
authors.forename: E
authors.initials: E
authors.lastname: Wakabayashi
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: E
authors.initials: E
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics*; D009206:Myocardium / Q000166:cytology; D009363:Neoplasm Proteins; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C109646:SSPN protein, human; C491632:Sspn protein, mouse; D049030:Dystroglycans