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Cutting Edge: The Y Chromosome Controls the Age-Dependent Experimental Allergic Encephalomyelitis Sexual Dimorphism in SJL/J Mice¹

Karen M. Spach^*, Melissa Blake^*, Janice Y. Bunn, Ben McElvany^*, Rajkumar Noubade^*, Elizabeth P. Blankenhorn and Cory Teuscher^2,*,

^* Department of Medicine, Department of Medical Biostatistics, and Department of Pathology, University of Vermont, Burlington, VT 05405; and Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129

Multiple sclerosis is a sexually dimorphic, demyelinating disease of the CNS, and experimental allergic encephalomyelitis (EAE) is its principal autoimmune model. Young male SJL/J mice are relatively resistant to EAE whereas older males and SJL/J females of any age are susceptible. By comparing a wide age range of proteolipid protein peptide 139–151 immunized mice, we found that female disease severity remains constant with age. In contrast, EAE disease severity increases with age in SJL/J males, with young males having significantly less severe disease and older males having significantly more disease than equivalently aged females. To determine whether the Y chromosome contributes to this sexual dimorphism, EAE was induced in consomic SJL/J mice carrying a B10.S Y chromosome (SJL.Y^B10.S). EAE was significantly more severe in young male SJL.Y^B10.S mice compared with young male SJL/J mice. These studies show that a Y chromosome-linked polymorphism controls the age-dependent EAE sexual dimorphism observed in SJL/J mice.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Multiple Sclerosis Society Grant RG3575 (to E.P.B. and C.T.) and National Institutes of Health Grants NS36526 (to C.T. and E.P.B.), NS061014 (to C.T.), and NS060901 (to C.T. and E.P.B.).

² Address correspondence and reprint requests to Dr. Cory Teuscher, C317 Given Medical Building, University of Vermont, Burlington, VT 05405. E-mail address: c.teuscher{at}uvm.edu

³ Abbreviations used in this paper: MS, multiple sclerosis; Chr, chromosome; CDS, cumulative disease score; EAE, experimental allergic encephalomyelitis; ENC, encephalitogen; Ext, external; Int, internal; MBP_Ac1–11, myelin basic protein acetylated N-terminal peptide 1–11; MSCH, mouse spinal cord homogenate; PLP_139–151, proteolipid protein peptide 139–151.

⁴ The online version of this article contains supplemental material.