RGD Reference Report - Genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9. - Rat Genome Database

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Genome-wide linkage analysis of chronic relapsing experimental autoimmune encephalomyelitis in the rat identifies a major susceptibility locus on chromosome 9.

Authors: Dahlman, I  Jacobsson, L  Glaser, A  Lorentzen, JC  Andersson, M  Luthman, H  Olsson, T 
Citation: Dahlman I, etal., J Immunol 1999 Mar 1;162(5):2581-8.
RGD ID: 69712
Web Url: http://www.jimmunol.org/v162n5/2581/2581-abs-frame.html
Pubmed: PMID:10072499   (View Abstract at PubMed)

The immunization of inbred Dark Agouti (DA) rats with an emulsion containing homogenized spinal cord and CFA induces chronic relapsing experimental autoimmune encephalomyelitis (EAE), a disease with many similarities to multiple sclerosis. We report here the first genome-wide search for quantitative trait loci regulating EAE in the rat using this model. We identified one quantitative trait locus on chromosome 9, Eae4, in a [DA(RT1av1) x BN(RT1n)]F2 intercross showing linkage to disease susceptibility and expression of mRNA for the proinflammatory cytokine IFN-gamma in the spinal cord. Eae4 had a larger influence on disease incidence among rats that were homozygous for the RT1av1 MHC haplotype (RT1av1 rats) compared with RT1n/av1 rats, suggesting an interaction between Eae4 and the MHC. Homozygosity for the DA allele at markers in Eae4 and in the MHC was sufficient for EAE. Thus, Eae4 is a major genetic factor determining susceptibility to EAE in this cross of DA rats. In addition, there was support for linkage to phenotypes of EAE on chromosomes 1, 2, 5, 7, 8, 12, and 15. The chromosome 12 region has been shown previously to predispose DA rats to arthritis, and the chromosome 2 region is syntenic to Eae3 in mice. We conclude that Eae4 and probably the other identified genome regions harbor genes regulating susceptibility to neuroinflammatory disease. The identification and functional characterization of these genes may disclose critical events in the pathogenesis of multiple sclerosis; understanding these events could be essential for the development of new therapies against the disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Encephalomyelitis  IDA 69712 RGD 
multiple sclerosis  IDA 69712 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased inflammatory response  QTM 69712 RGD 
paresis  QTM 69712 RGD 
Objects Annotated

QTLs
Eae4  (Experimental allergic encephalomyelitis QTL 4)

Strains
BN  (BN)
DA  (DA)

Objects referenced in this article
QTL Iresp3 Immunoglobin response QTL3 Rattus norvegicus

Additional Information