Evidence that the Y chromosome influences autoimmune disease in male and female mice

C Teuscher, R Noubade, K Spach… - Proceedings of the …, 2006 - National Acad Sciences
C Teuscher, R Noubade, K Spach, B McElvany, JY Bunn, PD Fillmore, JF Zachary…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
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 F2
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×
BS intercross mice as compared with females from the three other birth crosses (BS× SB …
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 F2 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 × BS intercross mice as compared with females from the three other birth crosses (BS × SB, SB × SB, and SB × 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.
National Acad Sciences