DYSTROPHIN IS NOT ESSENTIAL FOR THE INTEGRITY OF THE CYTOSKELETON

Dystrophin is localized, in normal muscle fibers, on the cytoplasmic s urface of the sarcolemma. The function of this protein is not known bu t, according to its structure and intracellular distribution, it seems likely that dystrophin interacts with other cytoskeletal proteins to form a complex linkage between myofibrils, sarcolemma and extracellula r matrix. To evaluate the possibility that dystrophin deficiency induc es, per se, a disarray in the cytoskeleton, we studied three component s of this structure in muscle fibers of the dystrophic mdx mouse in a phase preceding the onset of necrosis. Vinculin, abundant in sarcolemm al structures called costameres, desmin, the principal component of in termediate filaments and nebulin, constituent of the so-called ''third filament'' within the sarcomere, were stained with the indirect immun ofluorescence technique in cryostat sections. The same monoclonal anti bodies were used in Western blots of proteins extracted from the same muscles. No difference was observed in the distribution or in the rela tive abundance of the three proteins, comparing muscles from 18 days-o ld mdx and control mice. Our results indicate that the lack of dystrop hin does not induce, per se, alterations in the structures linking the sarcolemma to the contractile apparatus. It is likely that the struct ural damage in dystrophin-less muscle fibers is initially confined to limited portions of the plasma membrane. These focal lesions, impairin g intracellular calcium homeostasis, can lead to muscle fiber necrosis .