Evidence that the Y chromosome influences autoimmune disease in male and female mice.
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 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.
Teuscher
Cory
C
Department of Medicine and Pathology and Medical Biostatistics, University of Vermont, Burlington, VT 05405, USA. c.teuscher@uvm.edu
Noubade
Rajkumar
R
Spach
Karen
K
McElvany
Benjamin
B
Bunn
Janice Y
JY
Fillmore
Parley D
PD
Zachary
James F
JF
Blankenhorn
Elizabeth P
EP
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D049109:Cell Proliferation; D003433:Crosses, Genetic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012737:Sex Factors; D014998:Y Chromosome