| Project/Area Number |
16590392
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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 |
Virology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
FUJISAWA Jun-ichi Kansai Medical University, Faculty of Medicine, Professor (40181341)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | ATL / HTLV-1 / NOG-SCID mouse / SCID-hu / HTLV-1 infected carrier / Hematopoietic cell transplantation / 感染モデルマウス / 臍帯血 / NOG / SCID / NOD / 骨髄移植 / SCIDマウス |
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| Research Abstract |
To investigate the development of ATL, we established a model mouse which retains human hematopoetic system with HTLV-1 infected T-lymphocytes.
1. Development of humanized SCID-hu mouse: SCID-hu mouse was established by the intra-bone marrow transplantation of NOG-SCID (NOD-SCID/IL2R γ-chain knock-out) mouse with CD133-positive hematopoietic stem cells isolated from human cord blood. A major part of the bone marrow cells (average 72.3%) in SCID-hu mouse was replaced by human CD45 (+) cells after 2 months of transplantation and the normal development of human hematopoietic lineage cells including T-lymphocytes was observed.
2. HTLV-1 infection of humanized mouse: SCID-hu mouse was injected intra-peritonially with the γ-ray-irradiated HTLV-1 infected human T-cell line MT-2 and found infected in terms of the integration of HTLV-1 provirus into cellular genome of human T-cells in the SCID-hu mouse. The splenomegaly and an increase in the number of CD4 (+) T lymphocytes were observed in the infected SCID-hu mouse. Furthermore, more than 90% of the CD4 (+) T lymphocytes was composed of CD25 (+) cells, which is known as a main reservoir for HTLV-1 infected cells in HTLV-1 infected human carrier as well as ATL cells.
Since the HTLV-1 infected T-lymphocytes in the SCID-hu mouse exhibited an ATL-like overgrowth, this mouse model should provide a valuable system for the development of prevention and treatment of ATL.
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