| Project/Area Number |
63880012
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KATSURA Yoshimoto Kyoto Univ., Chest Dis.Res.Inst., Professor, 胸部疾患研究所, 教授 (90027095)
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| Co-Investigator(Kenkyū-buntansha) |
ISOBE Ken-ichi Nagoya Univ., Faculty of Medicine Associate Prof., 医学部, 助教授 (20151441)
FUJIMOTO Shinji Kyoto Univ., Chest Dis.Res.Inst., Assistant Prof., 胸部疾患研究所, 助手 (60199370)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1989: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1988: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | AIDS / Model animal / CD4 gene / Human immunodeficiency virus / Gene therapy / Transgenic mouse / Antisense RNA |
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| Research Abstract |
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).
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