Optimization of an animal model of experimental autoimmune encephalomyelitis achieved with a multiple MOG(35-55)peptide in C57BL6/J strain of mice.
The severity of the experimental autoimmune encephalomyelitis (EAE) induced by peptide myelin oligodendrocyte glycoprotein(35-55)(pMOG(35-55)) is thought to be predominantly influenced by the major histocompatibility complex (MHC), so that C57BL6/J mice, on H2(b) strain, were only mildly sick. However, it remains unclear as to how non-MHC gene regions affect EAE. To determine whether the immunization protocol could have an influence on clinical signs, C57BL6/J mice were immunized with a multiple antigen peptide (MAP) containing eight pMOG(35-55)branches synthesized directly onto a lysine core, myelin oligodendrocyte glycoprotein (35-55)-multiple antigen peptide (MOG(35-55)-MAP), in complete Freund's adjuvant (CFA). In most of the mice, clinical onset (marked weakness) occurred approximately at day 15. All mice injected with MOG(35-55)-MAP had more severe symptoms than those injected with pMOG(35-55), which developed no leg paralysis. All MOG(35-55)-MAP-immunized mice developed EAE symptoms, but 50% had primary-progressive EAE, while the other 50% had relapsing-remitting disease. Leukocyte infiltrations, associated with increased glial fibrillary acidic protein (GFAP) expression by reactive astrocytes, were observed around the lateral ventricles and blood vessels in the brain. Significant positive correlations were established between anti-MOG(35-55)antibody levels and clinical scores or GFAP positivity in the spinal cord. The heterogeneity of EAE progression, observed in these genetically identical individuals, suggests that the environment rather than the genetics plays a role. This observation is highly pertinent as it corresponds to what is seen in clinical MS.
Costa
Odile
O
INSERM U-519 and IFRMP 23, Faculté de Médecine et de Pharmacie, 22 Boulevard Gambetta, F-76183 Rouen Cedex 1, France. odile.costa@univ-rouen.fr
Divoux
Didier
D
Ischenko
Alexander
A
Tron
François
F
Fontaine
Marc
M
D000818:Animals; D000906:Antibodies / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology*
D000906:Antibodies; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)