Résumé :
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Communication n° 548. Familial Hypertrophic cardiomyopathy (FHC) is a monogenic disorder inherited in an autosomal-dominant fashion. FHC is related to mutations in at least 13 human genes, including MYBPC3 encoding the human cardiac myosin binding protein C (cMyBP-C) and responsible for 40% of FHC. Nevertheless, the molecular mechanisms involved are still poorly documented. In a previous study, we combined heterologous transgenesis with microarray analysis to approach the in vivo consequences of the expression of different human cMyBP-C protein forms in Drosophila melanogaster. The expression of the human protein is targeted in the indirect flight muscles (IFM), a tissue whose physiology is particularly close to human heart muscle. We observed a progressive age dependent flightless phenotype in transgenic flies expressing human cMyBP-C in IFM that results likely in the use of dysfunctional muscles. We identified over 90 deregulated genes in transgenic versus wild-type flies at day 8 after eclosion, using home made cDNA arrays containing 3600 genes. Among the functions associated to these 90 genes, there was a significant enrichment in processes linked to energetic and calcium metabolisms and muscle development. In order to complete this study, we held a time-course microarray experiment at day 1, 8 and 15 after adult eclosion using Affymetrix oligonucleotide arrays. This new transcriptome study covering the whole genome of Drosophila melanogaster will provide a dynamic overview of the gene deregulations and gene pathways associated with the acquisition and development of the phenotype. A few of them could be considered as new markers for the first identification of the evolving pathological process.
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