Genetic analysis of experimental allergic encephalomyelitis in mice.
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that exhibits many pathologic similarities with multiple sclerosis. While products of the MHC are known to control the development of EAE, it is clear that non-MHC products also influence susceptibility. The chromosomal locations of these were investigated in selective crosses between MHC class II-compatible, EAE-susceptible Biozzi ABH, and low responder nonobese diabetic (NOD) mice. The disease was dominant and highly influenced by gender in the backcross one (BC1) generation. Female mice were significantly more susceptible than male mice. Segregation of disease frequency of female animals in this cross suggested that EAE was controlled by a major locus. Although microsatellite-based exclusion mapping indicated that a number of regions on chromosomes 5, 6, 7, 8, 9, 10, 11, 12, 13, and 18 showed evidence of linkage (p < 0.05) compared with expected random distributions of alleles, disease susceptibility was most strongly linked (p < 0.001) to chromosome 7. However, by selectively analyzing animals that were either severely affected or almost normal, additional susceptibility loci were mapped on chromosomes 18 and 11 that were linked (p < 0.001) to resistance and the development of severe disease, respectively. The data indicate a major locus on chromosome 7, affecting initiation and severity of EAE that is probably modified by several other unlinked loci. These localizations may provide candidate loci for the analysis of human autoimmune-demyelinating disease.
Baker
D
D
Department of Clinical Ophthalmology, Royal College of Surgeons of England, London, United Kingdom.
Rosenwasser
O A
OA
O'Neill
J K
JK
Turk
J L
JL
D000818:Animals; D002874:Chromosome Mapping / Q000379:methods; D003433:Crosses, Genetic; D004276:DNA, Satellite / Q000032:analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains
D004276:DNA, Satellite