Altered a1-syntrophin expression in myofibers with Duchenne and Fukuyama muscular dystrophies

Abstract

a1-Syntrophin, a scaffolding adapter and modular protein, is a cytoplasmic component of the dystrophin glycoprotein complex. This study investigated immunohistochemically the expression of a1-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-a1-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-a1-syntrophin and rabbit anti-muscle-specific ßspectrin 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 a1-syntrophin-positive fibers and significant numbers of a1-syntrophinnegative fibers were present in dystrophin-positive muscles of severe muscular dystrophy such as FCMD. a-Dystrobrevin immunoreactivity was tested in DMD muscles and appreciable amounts of a-dystrobrevin that binds to syntrophin were found in DMD muscle membranes.