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Multiple linked quantitative trait loci within the Tmevd2/Eae3 interval control the severity of experimental allergic encephalomyelitis in DBA/2J mice

Genes & Immunity volume 11, pages 649–659 (2010)Cite this article

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Abstract

Theiler's murine encephalomyelitis virus-induced demyelination (TMEVD) and experimental allergic encephalomyelitis (EAE) are the principal animal models of multiple sclerosis (MS). Previously, we provided evidence that Tmevd2 and Eae3 may represent either a shared susceptibility locus or members of a gene complex controlling susceptibility to central nervous system inflammatory demyelinating disease. To explore the genetic relationship between Tmevd2 and Eae3, we generated a D2.C-Tmevd2 interval-specific congenic (ISC) line and three overlapping interval-specific recombinant congenic (ISRC) lines in which the Tmevd2-resistant allele from BALB/cByJ was introgressed onto the TMEVD-susceptible DBA/2J background. These mice, all H2d, were studied for susceptibility to EAE elicited by immunization with proteolipid protein peptide 180–199. Compared with DBA/2J mice, D2.C-Tmevd2 mice developed a significantly less severe clinical disease course and EAE pathology in the spinal cord, confirming the existence of Eae3 and its linkage to Tmevd2 in this strain combination. Compared with DBA/2J and D2.C-Tmevd2, all three ISRC lines exhibited clinical disease courses of intermediate severity. Neither differences in ex vivo antigen-specific cytokine nor proliferative responses uniquely cosegregated with differences in disease severity. These results indicate that multiple quantitative trait loci (QTLs) within the Tmevd2/Eae3 interval influence EAE severity, one of which includes a homology region for a QTL found in MS by admixture mapping.

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Acknowledgements

We thank Laura Cort and Meena Subramanian for technical support. This work was supported by the National Institutes of Health Grants NS36526 (CT), AI41747 (CT), AI058052 (CT), NS061014 (CT), NS060901 (CT) and AI45666 (CT) and by the National Multiple Sclerosis Society Grants RG3575 (EPB) and RG3575A5/1 (EPB).

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  1. K M Spach and L K Case: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, University of Vermont, Burlington, VT, USA

    K M Spach, L K Case, R Noubade, C B Petersen, B McElvany, N Zalik & C Teuscher

  2. Department of Pathology, Dartmouth Medical School, Hanover, NH, USA

    W F Hickey

  3. Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA

    E P Blankenhorn

  4. Department of Pathology, University of Vermont, Burlington, VT, USA

    C Teuscher

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Spach, K., Case, L., Noubade, R. et al. Multiple linked quantitative trait loci within the Tmevd2/Eae3 interval control the severity of experimental allergic encephalomyelitis in DBA/2J mice. Genes Immun 11, 649–659 (2010). https://doi.org/10.1038/gene.2010.40

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