DescriptionOligodendrocytes are an important cell type in the central nervous system (CNS). Their most prominent function in the brain is to provide axonal processes of neurons with insulation by means of creating myelin sheath that wrap around axons (myelination), which serves to increase the nerve conduction velocity, as well as to provide trophic support. Due to their high metabolic demand, oligodendrocytes are particularly susceptible to demyelinating pathology, the most prominent ones being multiple sclerosis and various leukodystrophies. Thus understanding the genetic and molecular factors that contribute to oligodendrocyte demyelination is crucial to our understanding of the diseases and identification of therapeutic targets. In order to address this issue, we conducted two studies in an attempt to elucidate the factors that are involved in regulation of the demyelination process in the CNS. Our first approach involves challenging two different mouse strains (C57BL/6 and CD1), which have different genetic backgrounds, with the neurotoxin cuprizone to induce a multiple sclerosis (MS)-like demyelinating pathology in the corpus callosum. We show that cuprizone induced demyelination is highly strain-dependent, and thus is under significant influence of genetic background factors. Our second approach involves probing the developmental as well as the cuprizone induced demyelinating phenotype in mice devoid of a gene that is highly expressed within CNS myelin, namely, Ephrin-B3. Our results suggest that Ephrin-B3 knockout animals exhibit relatively normal myelin-related phenotype compared to age-matched control animals, indicating that the gene is not specifically involved in regulation of oligodendrocyte myelination/demyelination in the CNS. Along the way, we document in this dissertation another separate study that aims to probe the developmental function of a gene named Fbxl15, which is a mammalian homolog of the drosophila jetlag gene, by way of gene-specific knockout study. We report here that Fbxl15 loss of function does not explicitly impact the circadian regulation in mice, and nor does it affect behavioral parameters in mice such as learning and memory, anxiety and depressive behavior. Thus we speculate that the function of Fbxl15 is redundant throughout development and that other F-box proteins could compensate for the absence of Fbxl15.