[Expression and localization of dystrophin during human skeletal, cardiac and smooth muscle development]

Dystrophin, the Duchenne muscular Dystrophy gene product, is a large cytoskeletal protein associated with a complex of membrane proteins, the Dystrophin Glycoprotein Complex (DGC). Dystrophin is localized to the sarcolemmal membrane of all normal muscle types, but is absent from muscles of DMD patients. Using monoclonal antibodies raised against distinct regions of the dystrophin, we studied its expression and subcellular localization during human skeletal, cardiac and smooth muscle development. We have shown that the expression and the association of dystrophin with the plasma membrane take place earlier in cardiac and smooth muscles (8 weeks of gestation) than in skeletal muscles. In skeletal muscles, dystrophin is first observed in the cytoplasm, and is progressively localized to the plasma membrane from 10 weeks onwards. We obtained differences in staining when using antibodies against either the central part of the protein or the carboxy-terminal domain, and we suggested that isoforms of dystrophin, probably differing in their carboxy-terminal end and their capacity to associate with the plasma membrane were differentially expressed during development and in different tissue-types (7). These findings are discussed in the context of the pathology of Duchenne Muscular Dystrophy.