title: Altered alpha1-syntrophin expression in myofibers with Duchenne and Fukuyama muscular dystrophies.
abstract: Alpha1-syntrophin, a scaffolding adapter and modular protein, is a cytoplasmic component of the dystrophin glycoprotein complex. This study investigated immunohistochemically the expression of alpha1-syntrophin in Duchenne and Fukuyama muscular dystrophies (DMD and FCMD, respectively). Biopsied muscles of five DMD, five FCMD, five normal controls and five disease controls (three myotonic and two facioscapulohumeral dystrophies) were analyzed. Immunoblot analysis showed that anti-alpha1-syntrophin antibody had a decreased reaction in both DMD and FCMD muscle extracts. Biopsied muscle sections and their serial sections were immunostained with rabbit anti-alpha1-syntrophin and rabbit anti-muscle-specific beta-spectrin antibodies, respectively. Immunoreactive patterns of sarcolemma were classified into (i) a continuously positive immunostaining pattern, (ii) a partially positive immunostaining pattern, (iii) a negative immunostaining pattern and (iv) a faint but entire surface positive immunostaining pattern. The group mean percentages of alpha1-syntrophin and beta-spectrin immunonegative myofibers in the DMD group were 39.3% and 10.8%, respectively, while those in the FCMD group were 45.5% and 10.4%, respectively. These values were statistically significant compared with those of disease control and normal control muscles. Thus we found that dystrophin-deficient DMD muscles contained significant numbers of alpha1-syntrophin-positive fibers and significant numbers of alpha1-syntrophin-negative fibers were present in dystrophin-positive muscles of severe muscular dystrophy such as FCMD. Alpha-dystrobrevin immunoreactivity was tested in DMD muscles and appreciable amounts of alpha-dystrobrevin that binds to syntrophin were found in DMD muscle membranes.
authors.affiliation: Department of Neurology, Showa University Fujigaoka Hospital, Yokohama, Japan. wakayama@showa-university-fujigaoka.gr.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Wakayama
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Jimi
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Kumagai
authors.forename: S
authors.initials: S
authors.lastname: Shibuya
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: H
authors.initials: H
authors.lastname: Oniki
mesh_terms: D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002462:Cell Membrane / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D049029:Dystrophin-Associated Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000737:chemistry*; D009124:Muscle Proteins / Q000032:analysis*; D009136:Muscular Dystrophies / Q000151:congenital* / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D009210:Myofibrils / Q000737:chemistry; D013049:Spectrin / Q000032:analysis
chemical_list: D002135:Calcium-Binding Proteins; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C098885:dystrobrevin; C091825:syntrophin alpha1; D013049:Spectrin