Spach Karen M, Blake Melissa, Bunn Janice Y, McElvany Ben, Noubade Rajkumar, Blankenhorn Elizabeth P, Teuscher Cory
Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
J Immunol. 2009 Feb 15;182(4):1789-93. doi: 10.4049/jimmunol.0803200.
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.
多发性硬化症是一种中枢神经系统的性别差异脱髓鞘疾病，实验性自身免疫性脑脊髓炎（EAE）是其主要的自身免疫模型。年轻的雄性SJL/J小鼠对EAE相对具有抗性，而老年雄性和任何年龄的SJL/J雌性小鼠都易感。通过比较广泛年龄范围的经蛋白脂质蛋白肽139 - 151免疫的小鼠，我们发现雌性疾病严重程度随年龄保持不变。相比之下，SJL/J雄性小鼠的EAE疾病严重程度随年龄增加，年轻雄性小鼠的疾病严重程度明显低于同龄雌性小鼠，而老年雄性小鼠的疾病则明显更严重。为了确定Y染色体是否导致这种性别差异，在携带B10.S Y染色体的同源SJL/J小鼠（SJL.Y(B10.S)）中诱导EAE。与年轻雄性SJL/J小鼠相比，年轻雄性SJL.Y(B10.S)小鼠的EAE明显更严重。这些研究表明，Y染色体连锁多态性控制了在SJL/J小鼠中观察到的年龄依赖性EAE性别差异。
