Physiological and biochemical analysis of VWF-cleaving protease ADAMTS13
| Project/Area Number |
17570126
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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 |
Functional biochemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
KOKAME Koichi National Cardiovascular Center Research Institute, Department of Vascular Physiology, Chief, 脈管生理部, 室長 (40270730)
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| Co-Investigator(Kenkyū-buntansha) |
BANNO Fumiaki National Cardiovascular Center Research Institute, Department of Vascular Physiology, Research Chief, 脈管生理部, 室員 (00373514)
MIYATA Toshiyuki National Cardiovascular Center Research Institute, Department of Vascular Physiology, Director, 病因部, 部長 (90183970)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | von Willebrand factor / ADAMTS13 / protease / enzyme / blood / platelet / thrombotic thrombocytopenic purpura / knockout mouse |
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| Research Abstract |
Plasma ADAMTS13 cleaves von Willebrand factor (VWF) multimers to regulate their activity in platelet aggregation. ADAMTS13 deficiency results in thrombotic thrombocytopenic purpura (TTP). The aim of this research is the production of clinically useful achievement through the basic analysis of ADAMTS13. [Analysis of ADAMTS13-deficient mice] Mice lacking the Adamts13 gene were generated. They showed a prothrombotic state but no symptoms of spontaneous thrombocytopenia, hemolytic anemia, and microvascular thrombosis. This suggested that a complete lack of ADAMTS13 in mice was not sufficient to cause TTP and other factors in addition to ADAMTS13 deficiency may be necessary for development of TTP. [Generation and analysis of congenic mice carrying truncated ADAMTS13] We previously identified two kinds of mouse ADAMTS13:129/Sv-strain ADAMTS13 with the same domains as human ADAMTS13 and C57BL/6-strain ADAMTS13 lacking the C-terminal multiple domains. To assess the significance of these domains in vivo, we generated and analyzed 129/Sv-genetic-background congenic mice that carry the C57BL/6-type ADAMTS13. [Biochemical and epidemiological analysis] Using a fluorescence-based assay, the biochemical features of ADAMTS13 were analyzed. The P475S form of ADAMTS13, frequently observed in the Japanese population, showed an approximately 70% activity of the wild type. [Search of ADAMTS13-interacting proteins] We used a yeast two-hybrid system to identify the candidates of ADAMTS13-interacting proteins, one of which was confirmed to bind directly to ADAMTS13. The present study provided new information about ADAMTS13, which will be useful for oncoming translational research.
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Report
(3 results)
Research Products
(48 results)
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[Journal Article] ADAMTS13の測定2006
Author(s)
小亀 浩市
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Journal Title
International Review of Thrombosis 1 (4)
Pages: 266-270
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
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[Book] 血栓症ナビゲーター2006
Author(s)
小亀 浩市
Total Pages
317
Publisher
メディカルレビュー社
Description
「研究成果報告書概要(和文)」より
Related Report
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