Application of microarray-based gene expression technology to neuromuscular disorders

Abstract

The work presented in this thesis describes the use of large-scale gene expression profiling to study muscle cell differentiation in health and in muscular dystrophies. A study is described exploring gene expression changes during muscle cell differentiation using human primary myoblast cell cultures (Chapter 3). Changes in expression levels immediately upon differentiation and up to day 4 were observed while the actual fusion of the cells started at the latter timepoint. Primary human myoblast cultures of Duchenne Muscular Dystrophy (DMD) patients were also shown to represent a good model system to study the impaired regeneration in this disease. Changes were found early in DMD myogenesis even before Dystrophin, the defective protein in DMD, is expressed (Chapter 4). To study another muscular dystrophy, oculopharyngeal muscular dystrophy (OPMD), we investigated gene expression changes in a cellular model overexpressing the mutant gene (PABPN1) (Chapter 5). In this cell-model inclusions occur in 20-80% of the nuclei. The results described in this thesis show that the application of gene expression profiling in the field of neuromuscular disorders yields new insights and theories.