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

该项目的目的是通过转基因抗碳水化合物抗体基因来建立自身免疫性神经病的模型小鼠。从本实验室建立的一系列分泌糖链特异性单抗的杂交瘤中，筛选出一株能与GD3、GD2、GD1b、GT1b、GQ1b等b通路神经节苷脂特异反应，而不与其他神经节苷脂或中性鞘糖脂反应的杂交瘤。首先，我们获得了抗神经节苷脂IgM抗体效价高的转基因小鼠。这些小鼠看起来很健康，在1岁时没有表现出明显的病理症状。接下来，我们试图通过用包括内毒素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，仅在血清中高滴度的神经节苷脂抗体不足以引起神经元症状。还需要进一步的研究来分析神经病变的机制。目前，我们正在培育抗体效价较高的转基因小鼠。

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.