Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18
| Autor: | Barbara Kornek, Lena Jacobsson, Christopher Linington, Erik Wallström, Hans Lassmann, Tomas Olsson, Ingrid Dahlman, Maria K. Storch, Robert Weissert, Holger Luthman |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Encephalomyelitis Autoimmune Experimental Genetic Linkage Encephalomyelitis Myelin oligodendrocyte glycoprotein Myelin Genetics medicine Demyelinating disease Animals Molecular Biology Genetics (clinical) Autoimmune disease biology Multiple sclerosis Experimental autoimmune encephalomyelitis Chromosome Mapping General Medicine medicine.disease Oligodendrocyte Rats Myelin-Associated Glycoprotein medicine.anatomical_structure Immunology biology.protein Female Myelin-Oligodendrocyte Glycoprotein Myelin Proteins |
| Zdroj: | Human molecular genetics. 8(12) |
| ISSN: | 0964-6906 |
| Popis: | 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 auto- immune 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 x ACI) F(2)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 chromosome 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. |
| Databáze: | OpenAIRE |
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