Multiple linked quantitative trait loci within the Tmevd2/Eae3 interval control the severity of experimental allergic encephalomyelitis in DBA/2J mice.
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.
Spach
K M
KM
Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
Case
L K
LK
Noubade
R
R
Petersen
C B
CB
McElvany
B
B
Zalik
N
N
Hickey
W F
WF
Blankenhorn
E P
EP
Teuscher
C
C
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics* / Q000276:immunology / Q000821:virology; D018188:Cardiovirus Infections / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics; D003711:Demyelinating Diseases / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D040641:Quantitative Trait Loci / Q000235:genetics*; D017945:Theilovirus
D005819:Genetic Markers; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments