Genetics. Published Articles Ahead of Print: November 19, 2005, Copyright © 2005
doi:10.1534/genetics.105.049049


A more recent version of this article appeared on February 1, 2006.

REGULAR RESEARCH PAPERS

eae36, A Locus on Mouse Chromosome 4 Controls Susecptibility to Experimental Allergic Encephalomyelitis in Older Mice and Mice Immunized in the Winter

Cory Teuscher 1*, Rebecca Doerge 2, Parley D. Fillmore 3 and Elizabeth Blenkenhorn 4

1 University of Vermont
2 Purdue
3 University of Illinois at Urbana-Champaign
4 Drexel University School of Medicine

* To whom correspondence should be addressed. E-mail: c.teuscher{at}uvm.edu.

Submitted on August 1, 2005
Revised on October 4, 2005
Accepted on 26 October 2005


Abstract

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 non-genetic 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 genome exclusion mapping based linkage analysis 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 eaa5 was not detected with the > 12-week-old and winter/spring populations. Rather, significant linkage to D4Mit203 at 60 cM 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.

Key Words: experimental autoimmune encephalomyelitis, gene and enviornmental interactions, genetic control, multiple sclerosis