Abstract |
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.
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Authors | M Jagodic, B Kornek, R Weissert, H Lassmann, T Olsson, I Dahlman |
Journal | Immunogenetics
(Immunogenetics)
Vol. 53
Issue 5
Pg. 410-5
(Jul 2001)
ISSN: 0093-7711 [Print] United States |
PMID | 11486278
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Autoantibodies
- MOG protein, human
- Mog protein, rat
- Myelin Proteins
- Myelin-Associated Glycoprotein
- Myelin-Oligodendrocyte Glycoprotein
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Topics |
- Animals
- Autoantibodies
(blood)
- Brain
(pathology)
- Chromosome Mapping
- Encephalomyelitis, Autoimmune, Experimental
(genetics)
- Genetic Predisposition to Disease
- Male
- Myelin Proteins
- Myelin-Associated Glycoprotein
(immunology)
- Myelin-Oligodendrocyte Glycoprotein
- Rats
- Rats, Inbred Strains
- Spinal Cord
(pathology)
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