P.3.3 MUC1 is associated with the pathogenesis of GNE-myopathy

Abstract

Distal myopathy with rimmed vacuoles (DMRV) is a genetic myopathy characterized clinically by distal muscle weakness, pathologically by the formation of inclusions and rimmed vacuoles. DMRV is caused by mutations of GNE, which regulates the synthesis of a sialic acid. Pathological findings of DMRV have already been reported to be improved by treatment with sialic acid metabolites. MUC1, which is one of transmembrane mucins, is associated with cell cycle, autophagy, and exocytosis. In this study, we examined MUC1 expression in DMRV and other neuromuscular disorders by immunohistochemical analysis and western blot analysis. The muscle biopsy specimens from DMRV (n = 6), sporadic inclusion body myositis (sIBM; n = 10), polymyositis (PM: n = 8), and normal control (NC: n = 5) were examined. These specimens were subjected to immunohistochemistry, immunofluorescent technique, and western blot, using antibodies against MUC1, and Aβ. In DMRVs, inclusions and RVs were immunopositive for MUC1 and Aβ, but the sarcolemma was not. On the other hand, the sarcolemma was also immunopositive for MUC1 in sIBM. In PM and NC, the pale immunoreactivity for MUC1 was observed only in the sarcolemma. Western blot indicated the decrease of MUC1 in DMRV. This study suggests that the decrease of MUC1 is implicated in the formation of aggregates and RVs in DMRV. The decrease of MUC1 might be associated with a hypoglycosylation due to decreased sialic acid synthesis.