Localisation of Dystrophin in skeletal muscle of mouse and man

Investigations aimed at a better understanding of the biochemical and physiological basis of Duchenne Muscular Dystrophy (DMD) have revealed that defects in a giant gene of 2.5 million basepairs are responsible for the phenotypic abnormalities described for patients with this disease. The 14 kb mRNA specifies a 400 kD muscular protein called ''dystrophin''. The abundance of this protein in healthy muscle cells is very low. It occupies only two thousands of a percent of the total protein content of these cells. To understand the relation between the absence of dystrophin in DMD affected muscle in man and MDX affected muscle in mice (a closely related disease) and the function of dystrophin in the ''healthy'' muscle of these species it is necessary to localise this protein on a subcellular level. With the use of the polyclonal antisera, raised against subfragments of dystrophin, that Hoffmann et al. (1987) used to demonstrate dystrophin in muscle cells, we have immunohistochemically demonstrated that in healthy individuals of both species this protein is localised in the sarcolemma of skeletal muscle cells while in MDX affected mice we were not able to demonstrate the presence of this protein. Besides the sarcolemmal distribution of dystrophin, we also detected a faint, but specific, staining with these antibodies in the sarcoplasma of muscle cells that expressed the fetal form of myosin heavy chain. In the skeletal muscle of the human fetus, dystrophin first appears at those sides of the muscle bundles where they are attached to the developing bones where it is localised in the sarcoplasma of these cells.