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Multiple loci comprising immune-related genes regulate experimental neuroinflammation.

Authors: Marta, M  Stridh, P  Becanovic, K  Gillett, A  Ockinger, J  Lorentzen, JC  Jagodic, M  Olsson, T 
Citation: Marta M, etal., Genes Immun. 2010 Jan;11(1):21-36. Epub 2009 Aug 13.
Pubmed: (View Article at PubMed) PMID:19675581
DOI: Full-text: DOI:10.1038/gene.2009.62

A 58 Mb region on rat chromosome 4 known to regulate experimental autoimmune encephalomyelitis (EAE) was genetically dissected. High-resolution linkage analysis in an advanced intercross line (AIL) revealed four quantitative trait loci (QTLs), Eae24-Eae27. Both Eae24 and Eae25 regulated susceptibility and severity phenotypes, whereas Eae26 regulated severity and Eae27 regulated susceptibility. Analyses of the humoral immune response revealed that the levels of serum anti-myelin oligodendrocyte glycoprotein (MOG) immunoglobin G1 (IgG1) antibodies are linked to Eae24 and anti-MOG IgG2b antibodies are linked to both Eae24 and Eae26. We tested the parental DA strain and six recombinant congenic strains that include overlapping fragments of this region in MOG-EAE. Eae24 and Eae25 showed significant protection during the acute phase of EAE, whereas Eae25 and Eae26 significantly modified severity but not susceptibility. The smallest congenic fragment, which carries Eae25 alone, influenced both susceptibility and severity, and protected from the chronic phase of disease. These results support the multiple QTLs identified in the AIL. By demonstrating several QTLs comprising immune-related genes, which potentially interact, we provide a significant step toward elucidation of the polygenically regulated pathogenesis of MOG-EAE and possibly multiple sclerosis (MS), and opportunities for comparative genetics and testing in MS case-control cohorts.


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CRRD Object Information
CRRD ID: 2317591
Created: 2010-04-12
Species: All species
Last Modified: 2010-04-12
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.