POLYGENIC CONTROL OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN BIOZZI ABH AND BALB C MICE/

Experimental allergic encephalomyelitis (EAE) is a chronic inflammator y disease of the central nervous system (CNS), with many similarities to multiple sclerosis (MS). Susceptibility to EAE is under genetic con trol of both the major histocompatibility complex (MHC) and unknown no n-MHC gene products. This study uses a selective cross between EAE-sus ceptible ABH and low responder BALB/c mice, where disease is dominant and affects female mice significantly more than males. In a genome scr een using microsatellite markers, linkage analysis suggests that genes encoded on chromosomes 4, 8, 10, 11, 12 and 17 contribute to the deve lopment of EAE (p < 0.05), although none of these putative EAE loci fu lfilled the criteria for significant linkage. Interestingly, genotype frequency showed significant deviation from the expected random distri bution of alleles on chromosomes 4, 8 and 17, (p < 0.001), with 32% of mice developing disease, exhibiting all 3 alleles (p < 0.001). This m ay indicate complex interactions amongst gene products in the EAE phen otype. This and other recent studies in different mouse strains underl ies that EAE is a complex polygenic trait and may provide clues to the genetic mechanisms involved in autoimmune diseases such as multiple s clerosis.