ROLE OF THE HIV-1 REGULATORY GENES IN TRANSGENIC MICE

描述：(改编自申请者的摘要)调查员将 尝试将相关的HIV基因导入小鼠的生殖系 获得转基因动物的意图，该转基因动物将在适当情况下发挥作用 HIV致病机制研究的模型。作者有 四个具体目标，第一个是确定艾滋病毒的作用(S) 调控基因Tat和nef通过各自的引入而诱导发病 它们中的每一个或组合，进入小鼠的生殖系。这个 第二个目标是针对特定的艾滋病毒调控基因，特别是 TAT基因，通过使用组织特异性来限制小鼠的细胞类型 转录调控元件以增强对 预期的疾病表型。第三个目标是试图理解 HIV潜伏和激活的机制与相互作用有关 病毒长末端重复序列与病毒和细胞之间的关系 反式激活剂。最后，调查员建议确定 环境因素的重要性，特别是其他人类病毒(如 如JC病毒和人类乙肝病毒)，在诱导HIV致病中 转基因小鼠。

DESCRIPTION: (Adapted from applicant's abstract) The investigator will attempt to introduce relevant HIV genes into the germline of mice with the intent of deriving transgenic animals which will serve as appropriate models for the study of mechanisms of HIV pathogenesis. The author has four specific aims, the first of which is to define the role(s) of the HIV regulatory genes, tat and nef, in inducing pathogenesis by introducing each of them individually, or in combination, into the germline of mice. The second goal is to target specific HIV regulatory genes, particularly the tat gene, to restricted cell types in mice by the use of tissue-specific transcriptional control elements in order to enhance the detection of anticipated disease phenotypes. The third goal is to try to understand the mechanism of HIV latency and activation as it pertains to the interaction between the viral LTR (long terminal repeat) and viral and cellular trans-activators. Lastly, the investigator proposes to ascertain the importance of environmental factors, particularly other human viruses (such as JC virus and human hepatitis B virus), in inducing HIV pathogenesis in transgenic mice.