Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 21, Pages 8024-8029Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0600536103
Keywords
autoimmunity; sex chromosomes disease susceptibility; parent-of-origin
Categories
Funding
- NIAID NIH HHS [AI4515, AI45666, AI41747, P01 AI045666, R01 AI041747] Funding Source: Medline
- NINDS NIH HHS [NS36526, R01 NS036526] Funding Source: Medline
- CSR NIH HHS [RG-3129] Funding Source: Medline
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Experimental allergic encephalomyelitis (EAE), an autoimmune model of multiple sclerosis, is a complex disease influenced by genetic, intrinsic, and environmental factors. In this study, we questioned whether parent-of-origin effects influence EAE, using reciprocal F-2 intercross progeny generated between EAE-susceptible SJL/J (S) and EAE-resistant B10.S/SgMcdJ (B) mice. EAE susceptibility and severity were found to be different in female BS x BS intercross mice as compared with females from the three other birth crosses (BS x SB, SB x SB, and SB x BS), and in fact, both traits in female mice resembled those of their male siblings. This masculinization is associated with transmission of the SJL/J Y chromosome and an increased male-to-female sex ratio. Related studies using progeny of C57BL/6J Y-chromosome substitution strains demonstrate that the Y chromosome again influences EAE in both male and female mice, and that the disease course in females resembles that of their male littermates. Importantly, these data provide experimental evidence supporting the existence of a Y-chromosome polymorphism capable of modifying autoimmune disease susceptibility in both males and females.
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