Genetics of experimental allergic encephalomyelitis

Abstract

The identification of genetic factors that control the pathogenetic pathways of autoimmune neuroinflammation and degeneration may provide targets for new therapeutic strategies in human diseases, such as multiple sclerosis. This is not easily accomplished as significant heterogeneity exists and such genetic dissection may more easily be performed using inbred rodent strains, where the genetic heterogeneity is avoided and variation in the environmental influences is minimized. Chronic relapsing experimental autoimmune encephalomyelitis (EAE) exhibits some histopathological features typical of multiple sclerosis and provides a tool to systemically identify genetic influences controlling susceptibility through genome scanning and selective breeding of congenic animals harbouring disease-related loci. As with MS, susceptibility is controlled by expression of certain major histocompatibility complex allotypes, which in EAE is in response to induction with certain myelin antigens. Both are complex polygenic diseases where disease traits are controlled by a number of polymorphic genes which individually exhibiting modest effect on disease course. A number of as yet largely unknown genes, cluster in certain regions that are sometimes shared between different strain combinations and are also shared by other inflammatory diseases, as they are uncovered the biology understood they may open avenues to treatment.