Congenic mapping confirms a locus on rat chromosome 10 conferring strong protection against myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.
Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in rats closely mimics the human disease multiple sclerosis (MS). As in MS, genetic predisposition to MOG-EAE is regulated by both MHC and non-MHC genes. Based on disease regulatory influences on MOG-EAE on chromosome 10 in an F2 cross between susceptible DA and resistant ACI rats, we have now isolated this locus in a congenic rat strain to enable further dissection of disease mechanisms. This region is of particular interest, since it is homologous to human 17q for which human whole-genome scans have indicated harbors genes regulating susceptibility to MS. Phenotypic comparison between DA and the congenic DA.ACI-D10Rat2-D10Rat29 strain confirms that the chromosomal segment harbors gene(s) conferring strong protection against MOG-EAE. Furthermore, resistance to EAE in this congenic strain is associated with absence or a low level of inflammation and demyelination in the central nervous system. Levels of anti-MOG antibody isotypes did not differ between parental and congenic rats, thus an action on Th1/Th2 differentiation is unlikely. In conclusion, this is the first example of an EAE-regulating locus isolated in a congenic rat strain with retained phenotype. The mechanism by which gene(s) in the region act is still unclear and will require further studies with this congenic rat strain as a tool.
Jagodic
M
M
Neuroimmunology Unit, Center for Molecular Medicine, L8:04, Karolinska Hospital, 17176 Stockholm, Sweden. maja.jagodic@cmm.ki.se
Kornek
B
B
Weissert
R
R
Lassmann
H
H
Olsson
T
T
Dahlman
I
I
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D008297:Male; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000473:pathology
D001323:Autoantibodies; C571326:MOG protein, human; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein