Evidence That the Y Chromosome Influences Autoimmune Disease in Male and Female Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 May 17

PMID 16702550

Citations 52

Authors

Cory Teuscher

Rajkumar Noubade

Karen Spach

Benjamin McElvany

Janice Y Bunn

Parley D Fillmore

James F Zachary

Elizabeth P Blankenhorn

Affiliations

Soon will be listed here.

Abstract

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.

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