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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
Journal article   Open access   Peer reviewed

Multiple Linked Quantitative Trait Loci within the Tmevd2/Eae3 Interval Control the Severity of Experimental Allergic Encephalomyelitis in DBA/2J Mice

Karen M Spach, Laure K Case, Rajkumar Noubade, Chase B Petersen, Ben McElvany, Nathan Zalik, William F Hickey, Elizabeth P Blankenhorn and Cory Teuscher
Genes and immunity, v 11(8), pp 649-659
Dec 2010
PMID: 20861860
url
https://doi.org/10.1038/gene.2010.40View
Published, Version of Record (VoR) Open

Abstract

EAE neuroimmunology genetics autoimmunity MS
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 CNS 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 H2 d , were studied for susceptibility to EAE elicited by immunization with PLP 180–199 . Compared to 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. Compare to 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 QTL 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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Collaboration types
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Web of Science research areas
Genetics & Heredity
Immunology
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