Journal Article

Linkage Analysis of Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis in the Rat Identifies a Locus Controlling Demyelination on Chromosome 18

Ingrid Dahlman, Erik Wallström, Robert Weissert, Maria Storch, Barbara Kornek, Lena Jacobsson, Christopher Linington, Holger Luthman, Hans Lassmann and Tomas Olsson

in Human Molecular Genetics

Volume 8, issue 12, pages 2183-2190
Published in print November 1999 | ISSN: 0964-6906
Published online November 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.12.2183
Linkage Analysis of Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis in the Rat Identifies a Locus Controlling Demyelination on Chromosome 18

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Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) with a complex etiology comprising a genetically determined predisposition and a suspected autoimmune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model for MS, which can be used to define susceptibility loci for autoimmune neuroinflammation. We have recently established a chronic relapsing EAE model characterized by inflammation and focal demyelination in the CNS by immunizing a variety of rat strains with the CNS-specific myelin oligodendrocyte glycoprotein (MOG). This model is more MS-like than any other rodent EAE model described up to now. Here we present the first systematic genome search for chromosomal regions linked to phenotypes of MOG-induced EAE in a (DA × ACI) F2 intercross. A genome-wide significant susceptibility locus linked to demyelination was identified on chromosome 18. This region has not been described in inflammatory diseases affecting other organs and the responsible gene or genes may thus be nervous system specific. Other chromosomal regions showing suggestive linkage to phenotypes of MOG-induced EAE were identified on chromosomes 10, 12 and 13. The chromo-some 10 and 12 regions have previously been linked to arthritis in DA rats, suggesting that they harbour immunoregulatory genes controlling general susceptibility to autoimmune diseases. We conclude that identification of susceptibility genes for MOG-induced EAE on rat chromosomes 10,12,13 and 18 may disclose important disease pathways for chronic inflammatory demyelinating diseases of the CNS such as MS.

Journal Article.  5006 words.  Illustrated.

Subjects: Genetics and Genomics

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