title: Reduced expression of sarcospan in muscles of Fukuyama congenital muscular dystrophy.
abstract: Expression profiles of sarcospan in muscles with muscular dystrophies are scarcely reported. To examine this, we studied five Fukuyama congenital muscular dystrophy (FCMD) muscles, five Duchenne muscular dystrophy (DMD) muscles, five disease control and five normal control muscles. Immunoblot showed reactions of sarcospan markedly decreased in FCMD and DMD muscle extracts. Immunohistochemistry of FCMD muscles showed that most large diameter myofibers expressed sarcospan discontinuously at their surface membranes. Immature small diameter FCMD myofibers usually did not express sarcospan. Immunoreactivity of sarcospan in DMD muscles was similarly reduced. With regard to dystroglycans and sarcoglycans, immunohistochemistry of FCMD muscles showed selective deficiency of glycosylated alpha-dystroglycan, together with reduced expression of beta-dystroglycan and alpha-, beta-, gamma-, delta-sarcoglycans. Although the expression of glycosylated alpha-dystroglycan was lost, scattered FCMD myofibers showed positive immunoreaction with an antibody against the core protein of alpha-dystroglycan. The group mean ratios of sarcospan mRNA copy number versus GAPDH mRNA copy number by real-time RT-PCR showed that the ratios between FCMD and normal control groups were not significantly different (P>0.1 by the two-tailed t test). This study implied either O-linked glycosylation defects of alpha-dystroglycan in the Golgi apparatus of FCMD muscles may lead to decreased expression of sarcoglycan and sarcospan molecules, or selective deficiency of glycosylated alpha-dystroglycan due to impaired glycosylation in FCMD muscles may affect the molecular integrity of the basal lamina of myofibers. This, in turn, leads to decreased expression of sarcoglycans, and finally of sarcospan at the FCMD myofiber surfaces.
authors.affiliation: Department of Neurology, Showa University Fujigaoka Hospital, Fujigaoka, Aoba-ku, Yokohama, Japan. wakayama@showa-university-fujigaoka.gr.jp
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Wakayama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kojima
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.forename: Seiji
authors.initials: S
authors.lastname: Shibuya
authors.forename: Takahiro
authors.initials: T
authors.lastname: Jimi
authors.forename: Hajime
authors.initials: H
authors.lastname: Hara
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Oniki
authors.forename: Motoi
authors.initials: M
authors.lastname: Kanagawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D049030:Dystroglycans / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D049031:Sarcoglycans / Q000096:biosynthesis / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C109646:SSPN protein, human; D049031:Sarcoglycans; D049030:Dystroglycans