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The Journal of Immunology, 2000, 164: 3420-3425.
Copyright © 2000 by The American Association of Immunologists

Genetic Analysis of the Influence of Pertussis Toxin on Experimental Allergic Encephalomyelitis Susceptibility: An Environmental Agent Can Override Genetic Checkpoints1

Elizabeth P. Blankenhorn2,*, Russell J. Butterfield{dagger}, Robert Rigby*, Laura Cort*, Dana Giambrone*, Paul McDermott*, Kay McEntee*, Nancy Solowski*, Nathan D. Meeker{dagger}, James F. Zachary{dagger}, Rebecca W. Doerge{ddagger} and Cory Teuscher{dagger}

* Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, PA 19129; {dagger} Department of Microbiology and Immunology, School of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802; and {ddagger} Department of Statistics, Purdue University, West Lafayette, IN 47907

Pertussis toxin (PTX) is a potent ancillary adjuvant used to elicit several different autoimmune diseases, including experimental allergic encephalomyelitis (EAE). To delineate the genetics of PTX effect in EAE, we mapped EAE-modifying (eae-m) loci in cohorts of backcross mice immunized with and without PTX. In this study, we analyzed the genetic basis of EAE susceptibility and severity and the intermediate phenotypes of mononuclear cell infiltration, suppuration, and demyelination. In animals immunized with PTX, one major locus, eae9, controls disease susceptibility and severity. Eae9 also regulates the extent of mononuclear cell infiltration of the spinal cord in male mice. Without PTX, five eae-m loci were noted, including three new loci in intervals on chromosomes 8 (eae14), 10 (eae17), and 18 (eae18). Taken together, these results suggest that eae9 controls the effects of PTX in EAE susceptibility, and is capable of overriding the other genetic checkpoints in the pathogenesis of this disease.




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