孤独症易感基因GRIN2B在神经元突触可塑性形成的功能研究

项目名称： 孤独症易感基因GRIN2B在神经元突触可塑性形成的功能研究

项目编号： No.31301023

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 许晓娟

作者单位： 中南大学

项目金额： 20万元

中文摘要： 孤独症是一种严重影响儿童健康的神经发育性疾病。其发病率在全球高达1%。孤独症的病因学及发病机制尚未阐明，流行病学调查显示遗传因素是孤独症的主要病因，包括染色体异常、拷贝数变异、罕见基因变异等。GRIN2B是近年来新发现与孤独症相关的基因。现有研究发现与孤独症相关的GRIN2B突变主要包括GRIN2B基因断裂和点突变。本研究前期工作中，我们通过传递不平衡和case-control分析, 发现GRIN2B基因与中国孤独症显著相关，并通过测序在孤独症患者中鉴定2个未报道的GRIN2B错义突变，提示GRIN2B是中国人群孤独症易感基因。GRIN2B是NMDA受体家族亚基之一，其编码的蛋白NR2B与NR1形成神经元递质门控离子通道，参与突触可塑性及学习记忆。本项目拟阐明突变体NR2B是否导致突触可塑性异常及参与孤独症发生的机制。

中文关键词： GRIN2B；孤独症；神经元；果蝇；

英文摘要： Autism is sever childhood neurodevelopmental disorders. By investigating, the prevalence is up to 1.0% worldwidely The etiology of autism is still unknown. Further more, autism is lack of effective therapy and the prognosis is not good. Epidemiological studies have shown that the the genetic factors are predominant in the pathogenesis of autism. Studies indicated that the Chromosome Abnormality, Copy Number Variations, rare mutation and so on are related to autism. More and more studies implied that GRIN2B was involved in the development of autism.It's reported that the GRIN2B mutations related to autism included the translocation breakpoint disrupting GRIN2B and the point mutation. In our study, we have found that GRIN2B is associated to autism by transmission disequilibrium test(TDT) analysis case-control analysis. Further we found two unreaported GRIN2B missense mutation. Our studied indicated that a possible role of GRIN2B as a candidate gene for the etiology of autism in Chinese Han population.GRIN2B is one of the NMDA subunits. Two NR1 subunits and two NR2 subunits form highly Ca2+ permeable cation channels which plays important roles in synaptic plasticity and in neuronal pattern formation during development. We suggest that the mutant NR2B may disrupt the neurotransmitter-gated ion channels which can c

英文关键词： GRIN2B；Autism；neuron；Drosophila；