Cellular and Molecular Biology


Altered alpha1-syntrophin expression in myofibers with Duchenne and Fukuyama muscular dystrophies

Y. Wakayama1, M. Inoue1, H. Kojima1, T. Jimi1, S. Yamashita2, T. Kumagai3, S. Shibuya1, H. Hara1 and H. Oniki4

1Department of Neurology and 4Electron Microscope Laboratory, Showa University Fujigaoka Hospital, Yokohama, Japan, 2Department of Neurology, Kanagawa Children’s Medical Center, Yokohama, Japan and 3Department of Pediatric Neurology, Aichi Prefectural Colony, Kasugai, Japan

Offprint requests to: Yoshihiro Wakayama, MD, PhD, Department of Neurology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, 227-8501 Japan. e-mail: wakayama@showa-university-fujigaoka.gr.jp

Summary. 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 ß-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 a1-syntrophin and ß-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. Histol Histopathol 21, 23-34 (2006)

Key words: alpha1-Syntrophin, Immunohistochemistry, Immunoblot, Skeletal myofiber, Human muscular dystrophies

DOI: 10.14670/HH-21.23