EXPRESSION AND SUBCELLULAR-LOCALIZATION OF DYSTROPHIN IN SKELETAL, CARDIAC AND SMOOTH MUSCLES DURING THE HUMAN-DEVELOPMENT

Dystrophin, the product of the DMD gene, is present in all muscle type s in normal individuals. Its function has yet to be elucidated, but it s absence or the presence of a truncated version of the protein is res ponsible for the appearance of Duchenne and Becker muscular dystrophie s. Using monoclonal antibodies raised against distinct regions of the dystrophin protein, we have examined its expression and subcellular di stribution during the human development in skeletal and smooth muscles . We show that both dystrophin expression and its association to the p lasma membrane take place earlier in cardiac and smooth muscles (8 wee ks of gestation) than in skeletal muscle. In skeletal muscle, dystroph in is first detected in the cytoplasm, and progressively localizes to the plasma membrane from 10 weeks onwards. Since we have obtained mark ed differences in staining when using antibodies against either a cent ral region of the protein or the C-terminal part, we suggest that diff erent fetal and adult dystrophin isoforms are expressed, probably diff ering in their C-terminal domain. These findings are discussed in the context of the pathology of Duchenne muscular dystrophy.