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

Genes Immun. 2010 Dec;11(8):649-59. doi: 10.1038/gene.2010.40. Epub 2010 Sep 23.


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 H2(d), 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics*
  • Animals, Genetically Modified / immunology
  • Animals, Genetically Modified / virology
  • Cardiovirus Infections / genetics
  • Chromosomes, Mammalian / genetics
  • Demyelinating Diseases / genetics*
  • Demyelinating Diseases / immunology
  • Demyelinating Diseases / virology*
  • Disease Models, Animal
  • Disease Susceptibility
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Myelin Proteolipid Protein / immunology
  • Peptide Fragments / immunology
  • Quantitative Trait Loci / genetics*
  • Theilovirus


  • Genetic Markers
  • Myelin Proteolipid Protein
  • Peptide Fragments