A Novel Mouse Model to Study Chronic‐Progressive Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory autoimmune disorder affecting the central nervous system (CNS) which affects over 400,000 Americans and over 2.5 million people worldwide. Although mostpatients are initially diagnosed with relapsing‐remitting MS, the majority of these patients later develop a chronic‐progressive form of MS, for which there is no well‐established mouse model. The most common genetic factors associated with genetic susceptibility to MS are the Human Leukocyte Antigen (HLA) genes which reside within the major histocompatibility gene complex (MHC), particularly in the HLA‐DR2b haplotype. Additionally, tumor necrosis factor alpha (TNF) signaling through the TNFR2 receptor has been shown to have an important role in the remyelination process and mice, deficient for TNFR2 have been shown to have increased disease severity. The aim of this project is to evaluate TNFR2‐/‐ mice, transgenic for the MS associated HLA‐DR2b haplotype, for their potential use as a model for chronic‐progressive MS. Our data indicates that the disease observed in HLA‐DR2b+/+ TNFR2‐/‐ mice closely mimics the pathology and clinical phenotype observed in chronic‐progressive MS. Currently we are further investigating the mechanisms that contribute to the disease phenotype in these mice. Thus, HLA‐DR2b+/+ TNFR2‐/‐ mice can be used to study chronic‐progressive MS and elucidate some of the mechanisms which are involved in the pathology of this disease.