Expression of the 43 kDa dystrophin-associated glycoprotein in human neuromuscular disease

Abstract

The expression of the 43 kDa dystrophin-associated glycoprotein (43DAG) has been studied using immunohistochemical labelling with a monoclonal antibody, MANDAG-1, and compared with immunolabelling for dystrophin and the dystrophin-related protein, utrophin, in normal muscle and in muscle from 50 patients with neuromuscular disease. 43DAG and dystrophin were expressed in vascular smooth muscle and at the sarcolemma of normal muscle fibres, with increased labelling at neuromuscular and myotendinous junctions. 43DAG expression was reduced in Duchenne and Becker dystrophies with patchy labelling, more intense around presumptive satellite cells. In Duchenne dystrophy, there was increased 43DAG expression in “revertant” fibres. In Becker dystrophy, 43DAG expression was more extensive around individual fibres, showed more interfibre variation and was more closely related to the intensity of immunolabelling for both dystrophin and utrophin than in Duchenne dystrophy. In other neuromuscular diseases, including congenital muscular dystrophy, no abnormalities of 43DAG expression were identified. The results suggest that in the absence of dystrophin, 43DAG is synthesized but is not stabilized in the sarcolemma. Stability is greater in Becker dystrophy but a normal dystrophin molecule appears to be required for the complete and stable membrane integration of 43DAG. Utrophin may confer some additional stability to the membrane integration of 43DAG but this is incomplete where dystrophin is absent or abnormal.