Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18
I. Dahlman et al., Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18, HUM MOL GEN, 8(12), 1999, pp. 2183-2190
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease
of the central nervous system (CNS) with a complex etiology comprising a g
enetically determined predisposition and a suspected autoimmune pathogenesi
s, Experimental autoimmune encephalomyelitis (EAE) is an animal model for M
S, which can be used to define susceptibility loci for autoimmune neuroinfl
ammation. We have recently established a chronic relapsing EAE model charac
terized by inflammation and focal demyelination in the CNS by immunizing a
variety of rat strains with the CMS-specific myelin oligodendrocyte glycopr
otein (MOG), This model is more MS-like than any other rodent EAE model des
cribed up to now. Here we present the first systematic genome search for ch
romosomal regions linked to phenotypes of MOG-induced EAE in a (DA x ACI) F
-2 intercross. A genome-wide significant susceptibility locus linked to dem
yelination was identified on chromosome 18, This region has not been descri
bed in inflammatory diseases affecting other organs and the responsible gen
e or genes may thus be nervous system specific, Other chromosomal regions s
howing suggestive linkage to phenotypes of MOG-induced EAE were identified
on chromosomes 10, 12 and 13, The chromo- some 10 and 12 regions have previ
ously been linked to arthritis in DA rats, suggesting that they harbour imm
unoregulatory genes controlling general susceptibility to autoimmune diseas
es. We conclude that identification of susceptibility genes for MOG-induced
EAE on rat chromosomes 10, 12, 13 and 18 may disclose important disease pa
thways for chronic inflammatory demyelinating diseases of the CNS such as M
S.