This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teuscher, C. Articles by Blankenhorn, E. P. Search for Related Content PubMed PubMed Citation Articles by Teuscher, C. Articles by Blankenhorn, E. P.

(American Journal of Pathology. 2004;165:1593-1602.)
© 2004 American Society for Investigative Pathology

Gender, Age, and Season at Immunization Uniquely Influence the Genetic Control of Susceptibility to Histopathological Lesions and Clinical Signs of Experimental Allergic Encephalomyelitis

Implications for the Genetics of Multiple Sclerosis

Cory Teuscher^*, Janice Y. Bunn, Parley D. Fillmore, Russell J. Butterfield, James F. Zachary and Elizabeth P. Blankenhorn

From the Departments of Medicine and Pathology^* and Medical Biostatistics, University of Vermont, Burlington, Vermont; the Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois; and the Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania

Multiple sclerosis (MS), the principal inflammatory demyelinating disease of the central nervous system (CNS), is believed to have an immunopathological etiology arising from gene-environment interactions. In this study, we examined the effect of sex, age, and season at immunization on the susceptibility of (B10.S x SJL/J) F₂ intercross mice to experimental allergic encephalomyelitis (EAE), the foremost animal model of MS. Results of logistic regression analyses suggest that female mice were more likely to exhibit CNS lesions than male mice [odds ratio (OR) = 2.28 for brain lesions; OR = 2.37 for spinal cord (SC) lesions]. Although statistically significant associations were seen between brain and SC lesions and age at the time of injection or month of injection when examined separately; these associations disappeared when controlling for sex in multiple logistic regression analyses. These results suggest that the sex of the mouse is more important in influencing the development of brain and SC lesions than was either age or month of immunization. When examining clinical disease as the endpoint, the OR for the age at immunization is 1.04, indicating that the odds of being affected increase by 4% for each increasing week of age. When controlled for age, the OR for injection in the summer months (July through September) is 1.90, suggesting that the odds of being clinically affected are 90% greater for F₂ intercross animals injected in the summercompared to those injected in the winter to spring months (February through May). In contrast to CNS lesions, the age and season at immunization significantly and independently influenced susceptibility to clinical EAE and did so equally in both males and females. Linkage analysis to eae5, the H2-linked locus controlling susceptibility to clinical disease, was performed using 6- to 12- and >12-week-old cohorts as well as summer and winter/spring cohorts of F₂ mice. Significant linkage of clinical EAE to eae5 was observed with the 6- to 12-week-old and summer populations. In contrast, linkage of clinical EAE to eae5 was not detected with the >12-week-old and winter/spring populations. These results indicate that age and seasonal effects are capable of overriding eae5-dependent genetic control of susceptibility to clinical EAE and have significant implications for the genetics of MS.

This article has been cited by other articles:

				K. M. Spach, M. Blake, J. Y. Bunn, B. McElvany, R. Noubade, E. P. Blankenhorn, and C. Teuscher Cutting Edge: The Y Chromosome Controls the Age-Dependent Experimental Allergic Encephalomyelitis Sexual Dimorphism in SJL/J Mice J. Immunol., February 15, 2009; 182(4): 1789 - 1793. [Abstract] [Full Text] [PDF]

				R. Goertsches, S. E Baranzini, C. Morcillo, C. Nos, M. Camina, J. R Oksenberg, X. Montalban, and M. Comabella Evidence for association of chromosome 10 open reading frame (C10orf27) gene polymorphisms and multiple sclerosis Multiple Sclerosis, April 1, 2008; 14(3): 412 - 414. [Abstract] [PDF]

				C. Teuscher, R. Noubade, K. Spach, B. McElvany, J. Y. Bunn, P. D. Fillmore, J. F. Zachary, and E. P. Blankenhorn Evidence that the Y chromosome influences autoimmune disease in male and female mice PNAS, May 23, 2006; 103(21): 8024 - 8029. [Abstract] [Full Text] [PDF]

				C. Teuscher, R. W. Doerge, P. D. Fillmore, and E. P. Blankenhorn eae36, a Locus on Mouse Chromosome 4, Controls Susceptibility to Experimental Allergic Encephalomyelitis in Older Mice and Mice Immunized in the Winter Genetics, February 1, 2006; 172(2): 1147 - 1153. [Abstract] [Full Text] [PDF]

				S. Jun, W. Gilmore, G. Callis, A. Rynda, A. Haddad, and D. W. Pascual A Live Diarrheal Vaccine Imprints a Th2 Cell Bias and Acts as an Anti-Inflammatory Vaccine J. Immunol., November 15, 2005; 175(10): 6733 - 6740. [Abstract] [Full Text] [PDF]