Generation of model mice for auto immune neuropathy by transfection with anti-carbohydrate chain antibody genes.

本项目旨在通过转染抗碳水化合物抗体基因建立自身免疫性神经病模型小鼠。在本实验室建立的一系列碳水化合物链特异性分泌单克隆抗体杂交瘤中，选择了一株产生单克隆抗体的杂交瘤，该单克隆抗体与b通路神经节苷类如GD3、GD2、GD1b、GT1b和GQ1b特异性反应，而不与任何其他神经节苷类或中性鞘糖脂反应。我们首先产生了具有高IgM抗体滴度的转基因小鼠。这些小鼠在1岁时看起来很健康，没有表现出明显的病理症状。接下来，我们尝试用包括LPS和细胞因子在内的多种佐剂免疫这些转基因小鼠来诱导神经病变。然而，他们没有表现出明显的症状。这些结果表明，仅血清中对神经节苷脂的高抗体滴度不足以诱导神经元症状。神经病变的发生机制有待进一步研究。目前，我们正在生产具有高IgG抗体滴度的转基因小鼠。

The aim of the project is to establish model mice for auto-immune neuropathy by transfection with anti-carbohydrate antibody genes. A hybridoma producing a monoclonal antibody, which reacts specifically with b-pathway gangliosides such as GD3, GD2, GD1b, GT1b, and GQ1b, but not with any other gangliosides or neutral glycosphingolipids was selected among a series of hybridomas secreting monoclonal antibodies specific for carbohydrate chains, that were established in our laboratory. We generated, at first, transgenic mice having high antibody titer of IgM to the ganglioides. These mice appeared to be healthy and exhibited no significant pathological symptoms at 1-year-old. Next, we tried to induce neuropathy by immunizing these transgenic mice with a number of adjuvants including LPS and cytokines. However, they showed no significant symptoms. These results suggest that only high antibody titer to the gangliosides in sera is not enough for inducing neuronal symptoms. Further study will be needed for analyzing the mechanisms of the neuropathy. At present, we are producing transgenic mice having high antibody titer of IgG.