New genetic loci that control susceptibility and symptoms of experimental allergic encephalomyelitis in inbred mice.
Experimental allergic encephalomyelitis (EAE), the principal animal model of multiple sclerosis, is a genetically determined phenotype. In this study, analyses of the cumulative disease frequencies in parental, F1 hybrid, and F2 mice, derived from the EAE-susceptible SJL/J strain and the EAE-resistant B10.S/DvTe strain, confirmed that susceptibility to EAE is not inherited as a simple Mendelian trait. Whole genome scanning, using 150 informative microsatellite markers and a panel of 291 affected and 390 unaffected F2 progeny, revealed significant linkage of EAE susceptibility to marker loci on chromosomes 7 (eae4) and 17, distal to H2 (eae5). Quantitative trait loci for EAE severity, duration, and onset were identified on chromosomes 11 (eae6, and eae7), 2 (eae8), 9 (eae9), and 3 (eae10). While each locus reported in this study is important in susceptibility or disease course, interactions between marker loci were not statistically significant in models of genetic control. One locus, eae7, colocalizes to the same region of chromosome II as Orch3 and Idd4, susceptibility loci in autoimmune orchitis and insulin-dependent diabetes mellitus, respectively. Importantly, eae5 and eae7 are syntenic with human chromosomes 6p21 and 17q22, respectively, two regions of potential significance recently identified in human multiple sclerosis genome scans.
Butterfield
R J
RJ
Department of Veterinary Pathobiology, University of Illinois, Urbana 61802, USA.
Sudweeks
J D
JD
Blankenhorn
E P
EP
Korngold
R
R
Marini
J C
JC
Todd
J A
JA
Roper
R J
RJ
Teuscher
C
C
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005819:Genetic Markers / Q000276:immunology; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology; D019655:Quantitative Trait, Heritable
D005819:Genetic Markers