Investigating susceptibility to demyelination in an Ermin deficiency-based model of multiple sclerosis

Multiple sclerosis (MS) is a chronic, typically progressive central nervous system (CNS) disease and one of the most common causes of neurological disability in young adults. The causes of MS are poorly understood, though components of autoimmune inflammation and an underlying degeneration of myelin and axons have been implicated in the disease. A great challenge in the MS field is to better understand disease progression and thus develop more effective therapies. Ermin, an actin-binding protein, has previously been linked to MS. Ermin is an actin binding protein specifically expressed in the myelin-producing oligodendrocytes that are compromised and break down in MS. Deficiency of Ermin has been linked to MS in both a multi-incident MS family and mouse models of MS. The goal of this project is to characterize the impact of Ermin deficiency on severity of demyelination and concurrent glial responses. Intrinsic dysfunction in myelin integrity caused by Ermin loss is expected to result in greater susceptibility to a demyelinating insult and greater expression of actin remodelling proteins. To test this hypothesis, I will subject C57BL/6 male and female wildtype (WT) and Ermin knockout (KO) mice to the cuprizone model of demyelination. I will examine the corpus callosum, the largest white matter region in the brain, for myelin markers, glial cell activation, and the SRF/MKL1 pathway to assess the extent of myelin damage. Results from this study could shed light on the role of Ermin in the maintenance of myelin integrity and the mechanisms of degeneration in the MS brain.