Résumé :
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Synemin is a linker protein, which form heteropolymer intermediate filaments with vimentin, desmin in the muscle or with neurofilaments, peripherins or GFAP in the nervous system. The synemin gene gives rise to three isoforms (H 180, M 150, L 41 kDa) through an alternative splicing mechanism. The different synemin isoforms interact with adhesion components vinculin, a-actinin, talin and dystrophin. We examined how synemin gene ablation induces morphological abnormalities and the consequences on the regeneration of muscle and the integrity of the neuromuscular junction. The synemin gene deletion induced no morphological abnormalities but a slight lean phenotype by significantly increasing lean mass content and tending to decrease fat mass content. Our results demonstrated that synemin knock out mice develop reduced specific maximal force and muscle fatigue resistance. Moreover, we observed a delay during muscle regeneration process induced by cardiotoxin. This was associated with a persistence of small diameter fibers containing developmental myosin isoforms. The muscle fibers of synemin knock out mice had a consistent accumulation of adipocytes. Thus the regenerating muscle fibers were smaller and stayed immature longer than those of wild type mice suggesting that the process of muscle regeneration is impaired. This work was supported by grants no. 13607 and 14848 from the Association Franse contre les Myopathies (AFM)
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