New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.
Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in rats that closely mimics many clinical and histopathological aspects of multiple sclerosis. Non-MHC quantitative trait loci regulating myelin oligodendrocyte glycoprotein-induced EAE have previously been identified in the EAE-permissive strain, DA, on rat chromosomes 4, 10, 15, and 18. To find any additional gene loci in another well-known EAE-permissive strain and thereby to assess any genetic heterogeneity in the regulation of the disease, we have performed a genome-wide linkage analysis in a reciprocal (LEW.1AV1 x PVG.1AV1) male/female F(2) population (n = 185). We examined reciprocal crosses, but no parent-of-origin effect was detected. The parental rat strains share the RT1(av1) MHC haplotype; thus, non-MHC genes control differences in EAE susceptibility. We identified Eae16 on chromosome 8 and Eae17 on chromosome 13, significantly linked to EAE phenotypes. Two loci, on chromosomes 1 and 17, respectively showed suggestive linkage to clinical and histopathological EAE phenotypes. Eae16 and Eae17 differ from those found in previously studied strain combinations, thus demonstrating genetic heterogeneity of EAE. Furthermore, we detected a locus-specific parent-of-origin effect with suggestive linkage in Eae17. Further genetic and functional dissection of these loci may disclose critical disease-regulating molecular mechanisms.
Becanovic
Kristina
K
Neuroimmunology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Wallstrom
Erik
E
Kornek
Barbara
B
Glaser
Anna
A
Broman
Karl W
KW
Dahlman
Ingrid
I
Olofsson
Peter
P
Holmdahl
Rikard
R
Luthman
Holger
H
Lassmann
Hans
H
Olsson
Tomas
T
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000276:immunology; D016678:Genome; D008297:Male; D018895:Microsatellite Repeats; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D040641:Quantitative Trait Loci; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001323:Autoantibodies; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein