Study of Generated trasgenic mice predominantly expressing T-tropic HIV-1

主要表达 T 向性 HIV-1 转基因小鼠的研究

基本信息

批准号：
10670279
负责人：
KOITO Atsushi
金额：
$ 1.66万
依托单位：
Kumamoto University (1999)University of Tsukuba (1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

We have generated transgenic mice predominantly expresing T-tropic HIV-1 receptors, human CD4 and CXCR4 on their CD4-positive T lymphocytes. Our data suggest that the dual function of CXCR4 in HIV-1 infection and in lymphocyte trafficking may cooperatvely induce progressive HIV-1 infection and CD4-positive T cell decline in patients.For understanding the pathogenesis of retroviral infection, it is necessary to identify the receptor molecule(s) which determine the host, tissue specificity of retrovirus replication. However, HIV-1 replication in these CD4 and CXCR4 double transgenic mice are found to be severely impared, limiting the use of mice in the studies for understanding the mechanism of HIV-1 pathogenesis in vivo. Preintegration forms of provirus are observed following infection of these mouse lymphoid cells, however the efficiency of integration into the chromosome of these cells were found to be much lower than that of human cell (Koito.A., Nagasawa.T., Suzuki.G., Matsushita.S., manuscript in preparation).Further studies are required to characterize the barrier exist mouse cells, and approaches to overcome the resistance of mouse lymphoid cells to human retrovirus infection may permit developing a rodent model that would present many obvious advantages. For identification of HTLV-1 receptor(s), we have generated cDNA libraries from activated human PBMC and packaged them into the retrovirus vector. Expression cloning of the molecules which involve in HYLV-1 infection is in progress.

我们已经在其CD4阳性T淋巴细胞上产生了转基因小鼠，主要阐明了T-热带HIV-1受体，人CD4和CXCR4。我们的数据表明，CXCR4在HIV-1感染和淋巴细胞运输中的双重功能可能会诱导患者的进行性HIV-1感染和CD4阳性T细胞下降。对于了解逆转录病毒感染的发病机理，确定受体分子的必要性是确定受体分子的必要性，这是确定宿主的重复，从而重复了逆转。然而，发现这些CD4和CXCR4双转基因小鼠中的HIV-1复制受到严重影响，从而限制了小鼠在研究中的使用，以理解体内HIV-1发病机理的机理。在感染这些小鼠淋巴样细胞后，观察到病毒的前整合形式，但是发现整合到这些细胞的染色体中的效率远低于人类细胞（Koito.A。，Nagasawa.t。，Suzuki.g，Suzuki.g。小鼠淋巴样细胞对人逆转录病毒感染的耐药性可能允许开发一种啮齿动物模型，该模型会带来许多明显的优势。为了鉴定HTLV-1受体，我们从活化的人PBMC中产生了cDNA文库，并将其包装到逆转录病毒载体中。涉及HYLV-1感染的分子的表达克隆正在进行中。