Résumé :
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Communication n° 167 Expansion of a polyalanine tract in the N-terminal region of the Poly(A)-Binding Protein Nuclear 1 (PABPN1) causes Oculopharyngeal Muscular Dystrophy (OPMD), a dominantly inherited, late onset disease. Ptosis, dysphagia and proximal limb weaknesses are the most common symptoms of OPMD. Despite the ubiquitous expression of PABPN1, the pathologic features of OPMD are restricted to skeletal muscle. The N-terminus of PABPN1 has been implicated in the activation of muscle specific genes but the mechanism by which the expansion results in a pathological phenotype and the selective engagement of skeletal muscle in OPMD is still not understood. In order to help clarifying the pathophysiology of OPMD, we constructed a cellular model of this disease by generating stable C2 cell lines expressing either wild-type or expanded PABPN1. Our first aim was to compare the differentiation capability of the wild-type and the OPMD cell lines. MyoD-dependent reporter gene activation was evaluated in the selected cell lines. Wild-type and expanded PABPN1-expressing cells displayed no differences in E-box-mediated transcription. We then determined the expression levels of early and late muscle differentiation markers by qRT-PCR. Similar levels of myogenic differentiation factors where observed at early and late differentiation stages when comparing wild-type and OPMD cell lines. These results suggest that myogenic differentiation is not impaired in OPMD. The global mRNA expression profiles of the wild-type and OPMD cell lines are currently being determined by microarray analysis. Identification of the differentially expressed genes will allow us to define cellular pathways altered in OPMD pathogenesis.
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