Résumé :
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Muscular dystrophies are characterized by a progressive weakness and degeneration of muscles. More than 30 distinct genetic defects causing muscular dystrophies have been identified, and many remain unknown. Current,therapeutic approaches aim at restoring the function of the implicated gene. Although such strategies are encouraging, they cannot be used as universal treatments for the large panel of muscular dystrophies. Thus, the identification of secondary defects common to different muscular dystrophies will identify new targets for future therapies or palliative treatments. In order to determine the cellular impairments or signaling pathways shared by different muscular dystrophies, we use the powerful genetic model organism Caenorhabditis elegans. We have established a library of 20 C. elegans models for muscular dystrophies caused by different primary genetic defects. In a first step, we have developped different subcellular markers to characterize the process of muscle degeneration in a C. elegans model for Duchenne Muscular Dystrophy (DMD) by electron and fluorescence microscopies, We are now using these markers to compare the degenerative process in the different C. elegans models and to identify common subcellular features for muscular dystrophies caused by different primary genetic defects. The most relevant subcellular markers will be used to identify pharmacological and genetic suppressors that can efficiently alleviate the phenotypes of all or a subset of the disease models.
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