Résumé :
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In recent years, large-scale 'omic' studies have helped to understand disease pathogenesis; however, these studies were done largely at the 'transcriptome' level. Understanding the biological processes at the protein level is also equally important. In general, mass spectrometry (MS)-based quantitative proteomic strategies are used to study protein alterations in different biological states. Among these strategies, stable isotope labeling by amino acids in cell culture (SILAC) is most widely used for comparative proteomics. In SILAC, proteins in cell populations are metabolically encoded with 'heavy' isotopes of lysine and arginine and are used as internal standards for relative quantification of differentially altered proteins. In this dissertation, the use of SILAC was extended to study in vivo proteomic modulations in mice. A stable isotope (13C-lysine)-labeled 'SILAC mouse' was generated in order to quantify and compare protein alterations between normal and pathological conditions... These studies not only provided information on the implicated pathways both in 'dystrophin-deficient' and 'myositis' muscle but also identified potential therapeutic targets. Nevertheless, future experiments will help to associate pathways identified using this proteomic strategy with gene expression profiling to comprehensively understand disease specific as well as general pathogenic pathways. These studies will pave the way to enhance development of improved therapies for these rare muscle diseases. (résumé de l'auteur)
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