Apparent alterations of erythrocyte acetylcholinesterase and other membrane proteins in Duchenne muscular dystrophy: a further example of a generalized membrane defect associated with hereditary muscular dystrophy.

The primary cause of genetically determined muscular dystrophy remains obscure. Evidence in favour of purely myopathic (Walton, 1969), neoronal (Gallup & Dubowitz, 1973), vascular (Hathway et al., 1970) and autoimmune (Jasmin & Bokdawala, 1970) mechanisms has been put forward. Attempts to find a mutant protein have not yet produced any substantial results. The increase that occurs in certain intracellular enzymes, such as creatine kinase, in the serum of patients with Duchenne muscular dystrophy (Pennington, 1969) may only indicate that the organization of plasma membrane with respect to its permeability is altered. A postulation, based on various observations (Das et al., 1971a,b; Rodan et al., 1974; Roses et al., 1975), strongly points to a generalized membrane defect as the fundamental problem in this disorder. To assimilate the different concepts on the lesion underlying this disease, we chose to investigate a functional protein that may be involved in maintaining normal neuromuscular activity. Acetylcholinesterase plays an important role in neuromuscular transmission (Nachmansohn, 1959). Since erythrocyte acetylcholinesterase appears to be similar (at least with respect to its substrate specificity) to the acetylcholinesterase at the neuromuscular junction and because the material is easily available, we have previously compared some properties of the enzyme in normal and diseased mice (Das et al., 1971a,b). In this presentation, we report further evidence confirming earlier observations on the altered properties of Triton X-100-solubilized erythrocyte acetylcholinesterase, which indicates membrane abnormality in Duchenne muscular dystrophy. Other erythrocyte-membrane enzymes (Brown et al., 1967; Roses et al., 1975) have also been reported to be altered in this disease. The possibility remains that the membrane defect in Duchenne muscular dystrophy can also be demonstrated when membrane constituents other than those already reported are investigated. For example, in spite of the reported similar protein pattern on sodium dodecyl sulphate/polyacrylamide-gel disc electrophoresis (Roses et at., 1975), we have observed different protein patterns of Triton-solubilized erythrocyte ‘ghosts’ from patients with Duchenne muscular dystrophy, on slab gel electrofocusing.