| Project/Area Number |
16390296
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Niigata University |
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Principal Investigator |
UCHIYAMA Makoto Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (80108050)
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| Co-Investigator(Kenkyū-buntansha) |
SATOKATA Ichiro Niigata University, Institute of Medicine and Dentistry, Professor, 医歯学系, 教授 (70170800)
ITO Tatsuo Niigata University, Institute of Medicine and Dentistry, Assistant, 医歯学系, 助手 (40345533)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | Alport syndrome / Alport syndrome model mice / bone marrow transplantation / gene therapy / Alport症候群 / Col4a4ノックアウトマウス / トランスジェニックマウス |
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| Research Abstract |
1.Examination of gene therapy by transplantating bone marrow derived stem cells of GFP mouse to Col4a4 knockout mice
(1)We demonstrated that allogeic bone marrow transplatation into irradiated COL4a4 knockout mice prepared as autosomal chromosome type Alport syndrome model mice by COL4A4 mutation, leaded, to recruitment of resident glomerular cells. In the present study, transplantation of green fluorescent protein (GFP) mouse's BM into 4-week-old and 8-week-old Col4a4 knockout mice leaded to recruitment of resident glomerular cells at 12 weeks of age.
(2)Type IV collagen a3 (COL4A3), a4 (COL4A4) and a5 (COLA5) chains were not detected in the glomerular basement membrane (GBM) after BMT by the immunohistochemistry.
2.Generating the transgenic mice overexpressing type IV collagen a3,4, and a5 chains in the bone marrow stem cells and transplantion of the bone marrow derived stem cell of the transgenic mice to Col4a4 knockout mice
(1)We generated the transgenic mice overexpressing type IV collagen a3,4, and a5 chains in the bone marrow cells. The survival and growth of the transgenic mice are not different from those of wild-type mice at present.
(2)Type IV collagen a3,a4 and a5 chains were not only detected in the GBM of the Col4a4 knockout mouse by the bone marrow transplantation of the GFP mouse but also the transgenic mouse's BMT.
3.Conclusions
Type IV collagen a3,a4 and a5 chains were not detected in the GBM after BMT. The bone marrow derived stem cells could recruit as endothelial cells and mesangial cells, but couldn't recruit as podocytes. Therefore it is thought that only podcytes may form the a3- a4- a5(IV) network in the GBM, or BMT leads to recruitment of very few glomerular cells.
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