RGD Reference Report - Resolution of a 16.8-Mb autoimmunity-regulating rat chromosome 4 region into multiple encephalomyelitis quantitative trait loci and evidence for epistasis. - Rat Genome Database

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Resolution of a 16.8-Mb autoimmunity-regulating rat chromosome 4 region into multiple encephalomyelitis quantitative trait loci and evidence for epistasis.

Authors: Jagodic, M  Marta, M  Becanovic, K  Sheng, JR  Nohra, R  Olsson, T  Lorentzen, JC 
Citation: Jagodic M, etal., J Immunol 2005 Jan 15;174(2):918-24.
RGD ID: 1547849
Pubmed: (View Article at PubMed) PMID:15634914

To investigate effects of a 16.8-Mb region on rat chromosome 4q42-43 on encephalomyelitis, we performed a high-resolution mapping using a 10th generation advanced intercross line between the susceptible DA strain and the MHC identical but resistant PVG.1AV1 strain. Clinical signs of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) developed in 29% of 772 F(10) rats. Three regions controlling disease, Eae20, Eae21, and Eae22, were mapped using 15 microsatellite markers spanning 16.8 Mb. Eae20 was a major genetic determinant within the region whereas Eae21 modified disease severity. Eae22 was identified as an epistatic region because it only displayed an effect together with Piebald Virol Glaxo (PVG) alleles on Eae20. Disease down-regulation by PVG alleles in the telomeric part of Eae20 was also demonstrated in DA rats made congenic for a approximately 1.44-Mb chromosomal region from PVG. As the region containing Eae20-Eae22 also regulates arthritis, together with the fact that the syntenic mouse 6F(2)-F(3) region regulates experimental lupus and diabetes, and the syntenic human 12p13.31-13.2 region regulates multiple sclerosis and rheumatoid arthritis, the present data point to genes that control several inflammatory diseases. The pairscan analyses of interaction, which here identified Eae22, are novel in the encephalomyelitis field and of importance in the design of further studies of this region in other diseases and species. The limited number of genes identified in Eae20, Eae21, and Eae22 enables focused examination of their relevance in mechanistic animal studies and screening of their association to human diseases.



Disease Annotations    


Objects Annotated

QTLs
Eae20  (Experimental allergic encephalomyelitis QTL 20)
Eae21  (Experimental allergic encephalomyelitis QTL 21)
Eae22  (Experimental allergic encephalomyelitis QTL 22)

Objects referenced in this article
Strain DA.PVG.1AV1-(D4Got128-D4Got136) null Rattus norvegicus
Strain DA.PVG.1AV1-(D4Rat63-D4Rat203) null Rattus norvegicus

Additional Information