| Project/Area Number |
11557182
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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 | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KOZUTSUMI Yasunori Gradeate school of biostudies, Kyoto University, Professor, 生命科学研究科, 教授 (70205425)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEMATSU Hiromu Graduate school of Biostudies, Kyoto University, lnstructor, 生命科学研究科, 助手 (80324680)
SUZUKI Akemi RIKEN Frontier, Group Director, フロンテイア研究システム, グループディレクター (70134533)
KAWASAKI Toshisuke Pharmaceutical Sciences, Kyoto University, Professor, 薬学研究科, 教授 (50025706)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | sialic acid / xenotransplantation / NeuGc / Siglec / CD22 / 臓器移植 / CMP-NeuAC水酸化酵素 / B細胞 / N-グリコリルノイラミン酸 / N-アセチルノイラミン酸 / シアル酸水酸化酵素 / ノックアウトマウス / ヒト化マウス |
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| Research Abstract |
During the grant period, we conducted a research to evaluate the carbohydrate antigen-medi-ated donor organ rejection in the proposed xenoplantation procedure. Recently, shortage of donor organs from human source for the transplantation made xenoplantation (non-human to human transplantation) a rationale source of donor organ to be transplanted to meet the demand. Here, porcine is expected as the logical choice of animal for the preparation of donor organs because of their similarity in size and relative higher amino- acid sequence homology between human. However these two animal species considerably differ for their expression of the carbohydrate antigens in their cell surface. To verify the antigenicty of the N-glycolylneuraminic acid (NeuGc) which human lacks, we developed the mouse line lacking functional CMP-N-acetylneuraminic acid hydroxylase gene. Major achie- vements in this study are as follows.
(1) The targeted mutagenesis of CMP-NeuAc hydroxylase re-created the lack of NeuGc in human that is known to lack active hydroxylase and its product NeuGc in cells.
(2) We analyzed the immune system development in these mice that may affect the point of organ rejection and found that this mouse line has normal immune system in steady state.
(3) We backcrossed this ES-based germline mutation to C57Black/6 line to prepare the donor organ for organ transplantation. Now the number of generations backcrossed is 17 and back- ground similarity between donor and recipient is expected to be quite strong concerning types of MHC and other protein-based antigens.
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