Congenic mapping confirms a locus on rat chromosome 10 conferring strong protection against myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis

Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune e ncephalomyelitis (EAE) in rats closely mimics the human disease multiple sc lerosis (MS). As in MS, genetic predisposition to MOG-EAE is regulated by b oth MHC and non-MHC genes. Based on disease regulatory influences on MOG-EA E on chromosome 10 in an F2 cross between susceptible DA and resistant ACI rats, we have now isolated this locus in a congenic rat strain to enable fu rther dissection of disease mechanisms. This region is of particular intere st, since it is homologous to human 17q for which human whole-genome scans have indicated harbors genes regulating susceptibility to MS. Phenotypic co mparison between DA and the congenic DA.ACI-D10Rat2-D10Rat29 strain confirm s that the chromosomal segment harbors gene(s) conferring strong protection against MOG-EAE. Furthermore, resistance to EAE in this congenic strain is associated with absence or a low level of inflammation and demyelination i n the central nervous system. Levels of anti-MOG antibody isotypes did not differ between parental and congenic rats, thus an action on Th1/Th2 differ entiation is unlikely. In conclusion, this is the first example of an EAE-r egulating locus isolated in a congenic rat strain with retained phenotype. The mechanism by which gene(s) in the region act is still unclear and will require further studies with this congenic rat strain as a tool.