Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice

beta-Sarcoglycan, one of the subunits of the sarcoglycan complex, is a tran smembranous glycoprotein which associates with dystrophin and is the molecu le responsible for beta-sarcoglycanopathy, a Duchenne-like autosomal recess ive muscular dystrophy. To develop an animal model of beta-sarcoglycanopath y and to clarify the role of beta-sarcoglycan in the pathogenesis of the mu scle degeneration in vivo, we developed beta-sarcoglycan-deficient mice usi ng a gene targeting technique. beta-Sarcoglycan-deficient mice (BSG(-/-) mi ce) exhibited progressive muscular dystrophy with extensive degeneration an d regeneration. The BSG(-/-) mice also exhibited muscular hypertrophy chara cteristic of beta-sarcoglycanopathy. Immunohistochemical and immunoblot ana lyses of BSG(-/-) mice demonstrated that deficiency of beta-sarcoglycan als o caused loss of all of the other sarcoglycans as well as of sarcospan in t he sarcolemma. On the other hand, laminin-alpha 2, alpha- and beta-dystrogl ycan and dystrophin were still present in the sarcolemma, However, the dyst rophin-dystroglycan complex in BSG(-/-) mice was unstable compared with tha t in the wild-type mice. Our data suggest that loss of the sarcoglycan comp lex and sarcospan alone is sufficient to cause muscular dystrophy, that bet a-sarcoglycan is an important protein for formation of the sarcoglycan comp lex associated with sarcospan and that the role of the sarcoglycan complex and sarcospan may be to strengthen the dystrophin axis connecting the basem ent membrane with the cytoskeleton.