Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region
Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region
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DOI：
10.1007/s00251-005-0066-1
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发表时间：
2006-02-01
期刊：
影响因子：
3.2
通讯作者：
Ridgway, WM
中科院分区：
文献类型：
--
作者：
Irie, J;Wu, YH;Ridgway, WM
抗史密斯抗体（anti-Sm）自身抗体针对小核核糖核蛋白（snRNP）家族中的蛋白质，被认为对人类和小鼠的系统性红斑狼疮（SLE）具有特异性。我们之前建立了NOD。c3c4小鼠，从3到4染色体携带B6和B10同源片段，具有非肥胖糖尿病（NOD）背景。仅在c4上携带B10片段的Idd9R28小鼠具有显著的抗sm抗体外显率。在这里，我们确定自身抗体在额外NOD中的发生率。Idd9同源菌株，并使用同源定位方法将增强自身抗体产生所需的间隔缩小到类似于含有胰岛素依赖型糖尿病（Idd）9.3的5.6 mb区域。Idd9.3区间包含分化候选分子簇（CD）137，它是肿瘤坏死因子（TNF）受体超家族的成员，作为T细胞的诱导共刺激剂，并控制T- b相互作用。NOD和B10 CD137等位基因对T细胞具有序列多态性和不同的功能作用；在CD137介导的共刺激后，NOD CD137等位基因介导较弱的T细胞增殖反应和减少白细胞介素(IL)-2的产生。我们的工作确定CD137是控制NOD.Idd9.3基因小鼠自身抗体产生的候选基因。
Anti-Smith (anti-Sm) autoantibodies are directed to proteins in the small-nuclear ribonucleoprotein (snRNP) family and are considered specific for systemic lupus erythematosus (SLE) in both humans and mice. We previously established that NOD.c3c4 mice, carrying B6 and B10 congenic segments from chromosomes 3 to 4 on an nonobese diabetic (NOD) background, and NOD.Idd9R28 mice, carrying a B10 segment on c4 alone, developed significant penetrance of anti-Sm antibody production. Here we determine autoantibody incidence in additional NOD.Idd9 congenic strains and use a congenic mapping approach to narrow the interval necessary for enhanced autoantibody production to a similar to 5.6-Mb region containing insulin-dependent diabetes (Idd)9.3. The Idd9.3 interval contains the candidate molecule cluster of differentiation (CD)137, which is a member of the tumor necrosis factor (TNF) receptor superfamily, functions as an inducible costimulator of T cells, and controls T-B interactions. The NOD and B10 CD137 alleles have sequence polymorphisms and different functional effects on T cells; the NOD CD137 allele mediates weaker T cell proliferative responses and decreased interleukin (IL)-2 production after CD137-mediated costimulation. Our work establishes CD137 as a candidate gene for control of autoantibody production in NOD.Idd9.3 congenic mice.