Gene-expression profiling of the early stages of MOG-induced EAE proves EAE-resistance as an active process.
Experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein (MOG) is a well-established animal model of multiple sclerosis (MS) in rodents. It reflects the wide spectrum of disease pathology and serves as a valuable tool for studying the pathogenesis and for testing new therapies of MS. In order to identify genes responsible for resistance to and modulation of the disease, we compared the mRNA expression profile of more than 12,000 genes by DNA microarray technique in lymph nodes of the highly EAE-susceptible mouse strain C57Bl/6 (B6) and the resistant strain C57Bl/10.S (B10). The disease onset in B6 mice was day 15. We identified 84 genes that were up-regulated more than two-fold in B10 mice compared to vehicle-treated controls, whereas only two genes were up-regulated in B6 mice after 7 and 15 days post-immunization (p.i.), respectively. We were able to match five up-regulated genes in B10 mice to known quantitative trait loci (QTLs), which control for EAE susceptibility. Only 17, respectively 5, genes were down-regulated at both time points in B10 and B6 mice. Tests for immunoreactivity to MOG (T cell proliferation and interferon-gamma (IFN-gamma) secretion) revealed no stronger immune response in B6 compared to B10 mice supporting the hypothesis of an immunosuppressive effect as a target to prevent EAE in the B10 mice. We conclude that resistance to EAE (and possibly to MS) is an active process mediated by multiple genes up-regulated in peripheral lymphatic organs of resistant animals. Thus, monitoring of the expression of these new candidate genes may serve as a tool for the disease progression and the pharmaceutical treatment.
Mix
Eilhard
E
Department of Neurology, University of Rostock, Gehlsheimer Str. 20, Rostock D-18055, Germany. eilhard.mix@med.uni-rostock.de
Ibrahim
Saleh
S
Pahnke
Jens
J
Koczan
Dirk
D
Sina
Christian
C
Böttcher
Tobias
T
Thiesen
Hans-Jürgen
HJ
Rolfs
Arndt
A
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000235:genetics; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma