Human CD4 gene transgenic mouse as an AIDS model animal.

本课题旨在建立人CD 4基因转基因小鼠作为艾滋病模型动物。这一目标实际上已经实现，尽管这项工作尚未完成，因为尚未证明小鼠T细胞上的人CD 4蛋白的表达。然而，CD 4转基因小鼠的一个关键问题是，其他研究小组已经建立了相同的转基因小鼠，并表明人类免疫缺陷病毒（HIV）在这种小鼠中没有感染。因此，我们发现没有科学意义的报告实验的细节。关于CD 4转基因小鼠的生产。因此，本文将介绍我们在艾滋病基因治疗基础研究中包括艾滋病模型动物的建立过程。艾滋病基因治疗的前提是找到或构建抗HIV基因。作为候选，我们采用了一个2.7kb的HIV基因组片段的反义构建体，该片段包括达特、rev和env的一部分。将该构建体转染到人CD 4 ^+ T细胞系CEM中，反义RNA得以表达，并且转染子显示出对HIV复制的抗性。目前我们正在建立将反义基因高效导入造血干细胞的方法，最近的研究表明，用HTLV-L病毒感染过的家兔对HIV感染敏感。此外，由于我们发现人CD 4基因转染兔T细胞系后，可显著提高兔T细胞系对HIV的敏感性，因此我们希望CD 4转基因兔能成为一种良好的艾滋病模型动物。这个项目正在进行中，作为一个与M博士合作。宫坂（医学科学研究所）。

The aim of this project is to establish a human CD4 gene transgenic mouse as an AIDS model animal. This aim was virtually achieved, although the work was not completed in that the expression of human CD4 protein on the mouse T cells has not yet been proven. A crucial problem for CD4 transgenic mouse, however, is that other research group has already established the same transgenic mouse and showed that human immiinodeficiency virus (HIV) did not infect in such mouse. Thus we fined no scientific importance to report the details of experiments. concerning the production of CD4 transgenic mouse. Therefore, we will report here about the whole story of our basic study on the gene therapy of AIDS in which the establishment of AIDS model animal is included.For the gene therapy of AIDS, it is prerequisite to find out or construct a HIV-resistant gene. As a candidate, we adopted an antisense construct of 2.7kb fragment of HIV genome including a part of tat, rev and env. Transfection of this construct into a human CD4^+ T cell line CEM resulted in expression of the antisense RNA, and the transfectants were shown to be resistant to HIV-replication. We are currently establishing the method to transfect the antisense gene into hemopoietic stem cells at high efficiency.It is recently shown that the rabbits which have previously been infected with HTLV-L virus are sensitive to HIV infection. Moreover, since we found that transfection of human CD4 gene into rabbit T cell line markedly augmented the HIV-sensitivity, we hope that CD4 transgenic rabbit will be a good AIDS model animal. This project is in progress as a cowork with Dr. M. Miyasaka (Metropolitan Institute of Medical Science).