Open AccessLoss of the Sarcoglycan Complex and Sarcospan Leads to Muscular Dystrophy in -Sarcoglycan-Deficient Mice
Author(s) -
Kenji Araishi,
Toshikuni Sasaoka,
Michihiro Imamura,
S. Noguchi,
Hiroshi Hama,
Eriko Wakabayashi,
Motoaki Yoshida,
Tetsuro Hori,
Eijiro Ozawa
Publication year - 1999
Publication title -
human molecular genetics online/human molecular genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.811
H-Index - 276
eISSN - 1460-2083
pISSN - 0964-6906
DOI - 10.1093/hmg/8.9.1589
Subject(s) - muscular dystrophy , dystrophin , biology , sarcolemma , itga7 , dystroglycan , laminin , utrophin , duchenne muscular dystrophy , microbiology and biotechnology , beta (programming language) , genetics , myocyte , extracellular matrix , computer science , programming language
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.