Genetic and Sex Steroid Hormone Contributions to the Sexual Dimorphism in Murine Experimental Allergic Encephalomyelitis
We found that the composition of the adjuvant used to induce EAE had important implications on the degree of genetic susceptibility necessary to result in disease. We also found that of the many quantitative trait loci (QTL) identified to date, genetic linkages to mouse chromosomes 7 and 11 were strongly associated with susceptibility to EAE. Further, the role of sex steroid hormones and parent-of-origin effects were studied through the use of reciprocal crosses of SJL/J and BI0.S/SgMcdJ mice. We found that adult gonadal hormones selectively regulate sexually dimorphic quantitative traits observed in EAE at the clinical, histopathologic, and genetic levels. Furthermore, we identified specific genetic linkages to chromosomes 3, 4, and 7 which were dependent on the presence or absence of gonadal sex steroids. These findings help explain the important roles of sex steroid hormones in the pathogenesis of EAE. By identifying genetic linkage in the context of specific immunologic and hormonal environments we have begun the process to identify specific genetic-environmental interactions underlying susceptibility to EAE.
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign