EXPRESSION OF THE 43 KDA DYSTROPHIN-ASSOCIATED GLYCOPROTEIN IN HUMAN NEUROMUSCULAR DISEASE

The expression of the 43 kDa dystrophin-associated glycoprotein (43DAG ) has been studied using immunohistochemical labelling with a monoclon al antibody, MANDAG-1, and compared with immunolabelling for dystrophi n and the dystrophin-related protein, utrophin, in normal muscle and i n muscle from 50 patients with neuromuscular disease. 43DAG and dystro phin were expressed in vascular smooth muscle and at the sarcolemma of normal muscle fibres, with increased labelling at neuromuscular and m yotendinous junctions. 43DAG expression was reduced in Duchenne and Be cker dystrophies with patchy labelling, more intense around presumptiv e satellite cells. In Duchenne dystrophy, there was increased 43DAG ex pression in ''revertant'' fibres. In Becker dystrophy, 43DAG expressio n was more extensive around individual fibres, showed more interfibre variation and was more closely related to the intensity of immunolabel ling for both dystrophin and utrophin than in Duchenne dystrophy. In o ther neuromuscular diseases, including congenital muscular dystrophy, no abnormalities of 43DAG expression were identified. The results sugg est that in the absence of dystrophin, 43DAG is synthesized but is not stabilized in the sarcolemma. Stability is greater in Becker dystroph y but a normal dystrophin molecule appears to be required for the comp lete and stable membrane integration of 43DAG. Utrophin may confer som e additional stability to the membrane integration of 43DAG but this i s incomplete where dystrophin is absent or abnormal.