Confocal analysis of the dystrophin protein complex in muscular dystrophy

The dystrophin protein complex (DPC), composed of at least 10 proteins that associate with dystrophin, is critical for the maintenance of normal muscl e fiber structure and physiology. In this study, we used immunohistochemist ry and confocal microscopy to examine the relative abundance and distributi on of several of these proteins in muscle biopsies taken from patients with various muscular dystrophies. The optical sectioning capability of confoca l microscopy allowed us to comprehensively analyze the semiquantitative exp ression of components of the DPC. Alpha-sarcoglycan-deficient patients disp layed a marked reduction in membrane immunostaining of the sarcoglycan comp lex. Gamma-sarcoglycan-deficient patients showed variable decreased immunos taining of the sarcoglycan complex proteins. When beta -sarcoglycan was exp ressed appropriately at the sarcolemma of gamma -sarcoglycan-deficient pati ents, intracellular labeling of beta -sarco-glycan was also present. Beta-s arcoglycan-deficient patients showed poor localization of extracellular mat rix proteins in addition to a complete absence of the sarcoglycans. Merosin -deficient patients showed relatively normal immunostaining levels of all o ther members of the DPC. Finally, dystrophin-deficient patients showed litt le or no change in the expression of extracellular matrix proteins; however , some sarcoglycans were significantly decreased. These data allowed us to suggest unique fundamental interactions between the members of the DPC. (C) 2001 John Wiley & Sons, Inc.