1998 Fiscal Year Final Research Report Summary
Attempt for gene therapy of retrovirus-induced disease
| Project/Area Number |
09670219
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
KITAGAWA Masanobu Tokyo Medical and Dental University, Faculty of Medicine Associate Professor, 医学部, 助教授 (10177834)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Retrovirus / Friend leukemia virus / Fv-4 / Gene therapy |
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| Research Abstract |
To develop the model for gene therapy of retrovirus-induced disease, Fv-4 resistance (Fv-4^r) gene which confers strong resistance against murine leukemia virus (MuLV)-infection to host has been introduced to Friend leukemia virus (FLV)-susceptible C3H mouse bone marrow cells.
1) Bone marrow transplantation of Fv-4^r-transfected bone marrow cells to C3H host
After introducing Fv-4^r gene using SFFV vector system, C3H bone marrow cells were transplanted to supralethally irradiated C3H host to create bone marrow chimeras (Fv-4^r-G3H * C3H). Fv-4^r gene product was expressed on the cell surface of hematopoietic cells in these chimera mice. The intensity of expression varied from mouse to mouse most of which expressed ranging from 10% to 20% of the expression by the hematopoietic cells of genetically Fv-4^r-bearing C4W mouse.
2) Development of gene induction system with high efficiency
By selecting vector systems and culture conditions, we could generate Fv-4^r-C3H * C3H chimeras that exhibited Fv-4^r expression of more than 30% of C4W mouse.
3) Trial experiment to test the resistance of these chimeras to FLV-infection
A few number of Fv-4^r-C3H * C3H chimeras with high expression of Fv-4^r (>30% of C4W) exhibited resistance against FLV inoculation of 1x103 PFU.However, all mice died after infection with lx 104 PFU of FLV.By using Fr-4^r-G3H * C3H chimeras with high expression of Fv-4^r which were successfully conducted in the latest experiments, we would be able to develop a better model system for retrovirus-induced disease.
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