Genetic analysis of susceptibility to experimental autoimmune encephalomyelitis in a cross between SJL/J and B10.S mice.
Experimental autoimmune encephalomyelitis (EAE), a model for human multiple sclerosis, is a T cell-mediated autoimmune disease that can be induced in experimental animals by immunization with myelin Ags. Inbred strains of mice show varying degrees of susceptibility to EAE, indicating that susceptibility is an inherited trait. To define the genetic factors that control susceptibility to EAE, we performed linkage analysis on the first backcross (BC1) between highly susceptible SJL/J mice and resistant B10.S mice, both of which are of the H-2s haplotype. Mice were immunized for disease with encephalitogenic myelin proteolipid protein peptide 139 to 151, and analysis was performed on 68 backcross mice showing the severe disease phenotype (disease score > or = 3)and 68 backcross mice of the resistant phenotype (no clinical or histologic signs of disease) using microsatellite markers covering >98% of the genome. We found the strongest linkage (p = 0.001) with clinical disease at two loci: one at the telomeric end of chromosome 2, and another near the center of chromosome 3. In addition, several other regions showing some evidence of linkage (p < or = 0.05) with clinical disease were found.
Encinas
J A
JA
Center for Neurologic Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Lees
M B
MB
Sobel
R A
RA
Symonowicz
C
C
Greer
J M
JM
Shovlin
C L
CL
Weiner
H L
HL
Seidman
C E
CE
Seidman
J G
JG
Kuchroo
V K
VK
D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D008040:Genetic Linkage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015431:Weight Loss / Q000235:genetics / Q000276:immunology