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Originally published as Genetics Published Articles Ahead of Print on November 19, 2005.
Genetics, Vol. 172, 1147-1153, February 2006, Copyright © 2006
doi:10.1534/genetics.105.049049
eae36, a Locus on Mouse Chromosome 4, Controls Susceptibility to Experimental Allergic Encephalomyelitis in Older Mice and Mice Immunized in the Winter
Cory Teuscher*,1,
R. W. Doerge
,
Parley D. Fillmore
and
Elizabeth P. Blankenhorn
* Departments of Medicine and Pathology, University of Vermont, Burlington, Vermont 05405, Departments of Agronomy and Statistics, Purdue University, West Lafayette, Indiana 47907, Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802 and Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129
1 Corresponding author: Immunobiology Program, C317 Given Medical Bldg., University of Vermont, Burlington, VT 05405.
E-mail: c.teuscher{at}uvm.edu
Genetic factors are believed to contribute to multiple sclerosis (MS) susceptibility; however, strong evidence implicating intrinsic and environmental factors in the etiopathogenesis of MS also exists. Susceptibility to experimental allergic encephalomyelitis (EAE), the principal animal model of MS, is also influenced by nongenetic factors, including age and season at immunization. This suggests that age- and season-by-gene interactions exist and that different susceptibility loci may influence disease as a function of the two parameters. In this study, linkage analysis based on genome exclusion mapping was carried out using age and season at immunization restricted cohorts of (B10.S x SJL/J) F2 intercross mice in an effort to identify such linkages. Significant linkage of EAE to eae4 and eae5 was detected with 6- to 12-week-old and summer cohorts. In contrast, significant linkage of EAE to eae4 and eae5 was not detected with the >12-week-old and winter/spring populations. Rather, significant linkage to D4Mit203 at 128.50 Mb on chromosome 4 was detected with animals that were >12 weeks old at the time of immunization or were immunized in the winter. This previously unidentified locus has been designated eae36. These results support the existence of age- and season-by-gene-specific interactions in the genetic control of susceptibility to autoimmune inflammatory disease of the central nervous system and suggest that late-onset MS may be immunogenetically distinct.
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