Duchenne Muscular Dystrophy (DMD) is a severe X-linked disease characterized by progressive muscle wasting and sometimes mild mental retardation. The disease is caused by mutations in the... Show moreDuchenne Muscular Dystrophy (DMD) is a severe X-linked disease characterized by progressive muscle wasting and sometimes mild mental retardation. The disease is caused by mutations in the dystrophin gene. DMD is correlated with the absence of Dp427, which is located along the sarcolemma in skeletal muscle where it is part of a large protein complex, the Dystrophin Glycoprotein Complex (DGC). A number of working hypotheses, based on studies from many laboratories, have been raised over the past decades, but the exact functions of the DGC are still largely unclear. The aim of our research is to dissect the fundamental, and likely evolutionarily conserved, functions of Dystrophin and the DGC in Drosophila. This thesis demonstrates different roles for Drosophila Dystrophin isoforms in the same tissue as well as apparently similar roles for two isoforms in different tissues. We have uncovered novel roles for two Dystrophin isoforms in regulating synaptic transmission via a retrograde signal. We now strive to uncover novel interacting proteins by further employing the powerful genetics of the fruit fly . These should help us further the understanding of the mechanisms leading to muscle degeneration and synaptic dysfunction, and may aid discovery of more effective treatments for Duchenne muscular dystrophy. Show less
