A genome-wide search identifies two susceptibility loci for experimental autoimmune encephalomyelitis on rat chromosomes 4 and 10

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis, The genetic loci that contribute to mononuclear cell i nfiltration of the central nervous system and clinical manifestations of EA E in the rat were investigated in the F-2 progeny of the highly susceptible Lewis and resistant Brown Norway strains. The data confirmed that the Lewi s allele of a MHC-Iinked gene is necessary, but not sufficient, to confer E AE susceptibility in the F-2 progeny. Subsequent analyses were thus restric ted to the subset of the F-2 animals with EAE-predisposing MHC genotypes. A genome-wide scan approach was performed using 103 microsatellite markers c overing 85% of the genome. Two non-MHC regions were identified, one near th e centromere of chromosome 4 and the other on the long arm of chromosome 10 , that significantly contributed to the disease. In addition, three regions on chromosomes 9, 13, and 17 were suggestive for linkage. Congenic mapping is now needed to reduce the support intervals encoding the loci of interes t to sizes amenable to physical mapping and to eventually demonstrate the i nvolvement of some of the candidate genes of immunologic importance localiz ed in these regions.