title: Eae19, a new locus on rat chromosome 15 regulating experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) and its animal model, myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), share a complex genetic predisposition with contributions from the major histocompatibility complex class II genes and many other genes. Linkage mapping in F(2) crosses between the susceptible DA rat strain and the resistant ACI or BN rat strains in various models of autoimmune neuroinflammation have repeatedly displayed suggestive linkage to a region on rat chromosome 15. A direct study of this region was undertaken in congenic strains by transferring resistant ACI alleles to the susceptible DA background. Phenotypic analysis demonstrated lower maximal and cumulative EAE scores in the DA.ACI-D15Rat6-D15Rat71 (C15), DA.ACI-D15Rat6-D15Rat48, D15Rat126-D15Rat71 (C15R3b), and DA.ACI-D15Rat23-D15rat71 (C15R4) strains compared to the parental DA rat strain. Linkage analysis was then performed in a (DA x PVG.AV1)F(7) advanced intercross line, resulting in a LOD score of 4.7 for the maximal EAE score phenotype at the peak marker D15Rat71 and a confidence interval of 13 Mb, overlapping with the congenic fragment defined by the C15R3b and the C15R4 strains. Thus, a new MOG-EAE locus with the designation Eae19 is identified on rat chromosome 15. There are 32 confirmed or predicted genes in the confidence interval, including immune-responsive gene 1 and neuronal ceroid lipofuscinose gene 5. Definition of loci such as Eae19 enables the characterization of genetically regulated, evolutionary conserved disease pathways in complex neuroinflammatory diseases.
authors.affiliation: Center for Molecular Medicine, Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.forename: Maja
authors.initials: M
authors.lastname: Jagodic
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dahlman
authors.forename: Kristina
authors.initials: K
authors.lastname: Becanovic
authors.forename: Rita
authors.initials: R
authors.lastname: Nohra
authors.forename: Monica
authors.initials: M
authors.lastname: Marta
authors.forename: Ellen
authors.initials: E
authors.lastname: Iacobaeus
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Erik
authors.initials: E
authors.lastname: Wallström
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D008040:Genetic Linkage; D016013:Likelihood Functions; D008126:Lod Score; D051381:Rats; D013997:Time Factors
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