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Congenic mapping confirms a locus on rat chromosome 10 conferring strong protection against myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis.

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.
AuthorsM Jagodic, B Kornek, R Weissert, H Lassmann, T Olsson, I Dahlman
JournalImmunogenetics (Immunogenetics) Vol. 53 Issue 5 Pg. 410-5 (Jul 2001) ISSN: 0093-7711 [Print] United States
PMID11486278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • MOG protein, human
  • Mog protein, rat
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
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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