Polygenic control of experimental allergic encephalomyelitis in Biozzi ABH and BALB/c mice.
Experimental allergic encephalomyelitis (EAE) is a chronic inflammatory disease of the central nervous system (CNS), with many similarities to multiple sclerosis (MS). Susceptibility to EAE is under genetic control of both the major histocompatibility complex (MHC) and unknown non-MHC gene products. This study uses a selective cross between EAE-susceptible ABH and low responder BALB/c mice, where disease is dominant and affects female mice significantly more than males. In a genome screen using microsatellite markers, linkage analysis suggests that genes encoded on chromosomes 4, 8, 10, 11, 12 and 17 contribute to the development of EAE (p < 0.05), although none of these putative EAE loci fulfilled the criteria for significant linkage. Interestingly, genotype frequency showed significant deviation from the expected random distribution 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 may indicate complex interactions amongst gene products in the EAE phenotype. This and other recent studies in different mouse strains underlies that EAE is a complex polygenic trait and may provide clues to the genetic mechanisms involved in autoimmune diseases such as multiple sclerosis.
Croxford
J L
JL
Department of Clinical Ophthalmology, Institute of Ophthalmology, University College London, UK.
O'Neill
J K
JK
Baker
D
D
D000818:Animals; D002874:Chromosome Mapping; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics*; D008815:Mice, Inbred Strains / Q000235:genetics*; D018895:Microsatellite Repeats