RGD Reference Report - Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18. - Rat Genome Database

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Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18.

Authors: Dahlman, I  Wallstrom, E  Weissert, R  Storch, M  Kornek, B  Jacobsson, L  Linington, C  Luthman, H  Lassmann, H  Olsson, T 
Citation: Dahlman I, etal., Hum Mol Genet 1999 Nov;8(12):2183-90.
RGD ID: 69695
Web Url: http://www.oup.co.uk/hmg/Volume_08/Issue_12/ddc249_gml.abs.html
Pubmed: PMID:10545597   (View Abstract at PubMed)

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) with a complex etiology comprising a genetically determined predisposition and a suspected auto- immune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model for MS, which can be used to define susceptibility loci for autoimmune neuroinflammation. We have recently established a chronic relapsing EAE model characterized by inflammation and focal demyelination in the CNS by immunizing a variety of rat strains with the CNS-specific myelin oligodendrocyte glycoprotein (MOG). This model is more MS-like than any other rodent EAE model described up to now. Here we present the first systematic genome search for chromosomal regions linked to phenotypes of MOG-induced EAE in a (DA x ACI) F(2)intercross. A genome-wide significant susceptibility locus linked to demyelination was identified on chromosome 18. This region has not been described in inflammatory diseases affecting other organs and the responsible gene or genes may thus be nervous system specific. Other chromosomal regions showing suggestive linkage to phenotypes of MOG-induced EAE were identified on chromosomes 10, 12 and 13. The chromosome 10 and 12 regions have previously been linked to arthritis in DA rats, suggesting that they harbour immunoregulatory genes controlling general susceptibility to autoimmune diseases. We conclude that identification of susceptibility genes for MOG-induced EAE on rat chromosomes 10, 12, 13 and 18 may disclose important disease pathways for chronic inflammatory demyelinating diseases of the CNS such as MS.



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Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Eae12Ratabnormal inflammatory response  QTM  RGD 
Eae14Ratabnormal inflammatory response  QTM  RGD 
Eae12Ratdemyelination  QTM  RGD 
Eae13Ratdemyelination  QTM  RGD 
Eae14Ratdemyelination  QTM  RGD 
Eae15Ratdemyelination  QTM  RGD 
Eae15Ratincreased inflammatory response  QTM  RGD 
Eae12Ratparesis  QTM  RGD 
Eae13Ratparesis  QTM  RGD 
Eae14Ratparesis  QTM  RGD 
Eae15Ratparesis  QTM  RGD 

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Objects Annotated

QTLs
Eae12  (Experimental allergic encephalomyelitis QTL 12)
Eae13  (Experimental allergic encephalomyelitis QTL 13)
Eae14  (Experimental allergic encephalomyelitis QTL 14)
Eae15  (Experimental allergic encephalomyelitis QTL 15)

Strains
ACI/N  (A X C 9935, Irish)
DA  (DA)


Additional Information