Alteration of the ganglioside composition of skeletal muscle in murine muscular dystrophy.

Abstract

MUSCULAR dystrophy in the mouse is a hereditary disorder which is considered to be a primary myopathy1–5. Reports that the reactions of the muscles of dystrophic mice to neostigmine and d-tubocurarine are similar to those of denervated muscle6, that about one-quarter of the fibres are functionally denervated7, that dystrophic muscle has fewer functional motor units and less motor nerve fibres than normal muscle8 and the transplantation studies of Salafsky9, suggest, however, that neural factors are important in this disease. We have reported that denervation of skeletal muscle results in an increase in the content of the major sialoglycolipid of skeletal muscle, N-acetylneuraminylgalactosylglucosylceramide, GM3 (named according to Svennerholm's ganglioside nomenclature)10. The increased level of GM3 was shown to result from de novo synthesis of this material. We therefore examined the ganglioside composition of skeletal muscle in hereditary mouse myopathy to look for an effect similar to that induced by denervation. Our data, however, indicate that the GM3 level is decreased in dystrophic muscle. The decrease is accompanied by an increase in the amounts of the higher ganglioside homologues.