Résumé :
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Communicatin n° 142 Introduction : The muscle histopathology of myotonic dystrophy type 2 (DM2) shows nuclear clump fibers, which have been considered as a hallmark of neurogenic atrophy. We have previously shown that these and other extremely small fibers in DM2 are identified as type 2 fibers, expressing fast myosin heavy chain (MHCf). These atrophic type 2 fibers occur early in DM2 proximal muscles, often before clinical muscle symptoms, which is in contrast to DM1. Objectives : To investigate the origin of the small type 2 fibers in DM2 we have used markers for muscle regeneration, denervation and satellite cells, in order to assess whether they have undergone an atrophic process, or if they might be of satellite cell origin. Methods : We used immunohistochemistry with antibodies against developmental and neonatal MHC (MHCd and MHCn); fast fiber -specific MHCf, Serca-1 and troponin-T; slow MHC; quiescent satellite cell marker CD34; myogenesis markers desmin, N-CAM and M-cadherin. Patient material consisted of frozen muscle biopsies from 20 DM2 patients, 4 DM1 patients, 4 patients with peripheral and 4 with central neurogenic atrophy. Serial sections and double staining for identification of expression patterns of individual fibers were used. Results : Most of the small type 2 fibers in both DM2 and neurogenic atrophy stained positively for MHCn, whereas only few fibers were MHCd positive. CD34 was not expressed, but many small fibers, including those with nuclear clumps, were N-CAM and desmin positive. Conclusions : The expression of MHCn but not MHCd in DM2 very small type 2 fibers, together with N-CAM up regulation, suggest that they do not result from a necrotizing process, but are rather induced by reprogramming which mimics neurogenic mechanisms of atrophy and results in appearance of nuclear clump fibers. However, other very small type 2 fibers might originate from satellite cells, which upon activation do not undergo the myogenic maturation program fully and correctly.
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