Human CD4 gene transgenic mouse as an AIDS model animal.

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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).