项目名称: 构建ASPP2/P53缺失的GP120转基因鼠研究HAD神经凋亡机制
项目编号: No.30870853
项目类型: 面上项目
立项/批准年度: 2009
项目学科: 轻工业、手工业
项目作者: 陈德喜
作者单位: 首都医科大学
项目金额: 34万元
中文摘要: 20 年来以西方国家用免疫缺陷病毒一型(HIV-1)gp120 蛋白的转基因小鼠模型研究HIV 相关痴呆(HAD)的机制主要集中在B 亚型。而我国已经发现11 种艾滋病毒流行株,非B 亚型占很大的比率。随着我国HIV 感染者临床发病高峰的来临,HAD 病人在临床上也越来越多见。但对该病的病理机制研究至今在我国仍是空白。我们最近的研究显示P53/ASPP2 在gp120 引起的细胞凋亡中起着重要的作用。因此为研究ASPP2/P53 在HIVgp120 引起神经细胞凋亡的机制,我们将构建表型为p53 纯合子缺失和ASPP2 杂合子缺失的星状胶质细胞特异表达GP120 的转基因小鼠模型。通过体内和体外实验研究我国主要流行亚型的gp120 所致HAD 发生发展机制和ASPP2/P53 表达的关系,本研究不仅将得到我国自主知识产权的转基因鼠,而且对于指导AIDS 的神经相关疾病的临床治疗具有重要的意义。
中文关键词: 艾滋病;糖蛋白120;P53;ASPP2;小鼠;
英文摘要: The human immunodeficiency virus type 1 (HIV-1) gp120 protein is a key pathogenic factor in a variety of acquired immune deficiency syndrome (AIDS)-associated disorders. A number of studies in HIV-1 neuropathogenesis with gp120 protein transgenic mouse model are mainly focus on the HIV_B subtype. Up to now 11 kinds of HIV subtype have been found in our Country and most of them are no B subtype. The pathogenesis of HAD is still unclear and our study showed that p53 and aspp2 may represent a final common pathway of neuron death in response to gp120 induced neurotoxins. To gain a better understanding of the roles of gp120 protein plays what kind of role in neuron death, we attempt to establish a gp120 transgenic mice in which gp120 expression was regulated by the astrocyte-specific glial fibrillary acidic protein promoter. The P53-/-ASPP2+/-GP120t mice will be produced after refeeding gp120 transgenic mice with p53 and ASPP2 knockout mice. The final purpose is to demonstrate a novel role for aspp2 and p53 in the neuron response to gp120.
英文关键词: AIDS; gp120; P53; ASPP2; mouse