2012 Fiscal Year Final Research Report
Generation and characterization of knock-in mice carrying the point mutations associated with thrombosis in Japanese
| Project/Area Number |
22790923
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
BANNO Fumiaki 独立行政法人国立循環器病研究センター, 研究所, 研究員 (00373514)
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| Project Period (FY) |
2010 – 2012
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| Keywords | プロテインS / プラスミノーゲン / ノックインマウス / 遺伝子変異 / 日本人の血栓症 / 血液凝固 / 線溶 |
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| Research Abstract |
The K196E mutation in protein S (PS) is found in one of 55 Japanese and is a genetic risk factor for vein thrombosis in Japanese. The A620T mutation in plasminogen (PLG) is found in one of 25 Japanese and causes decreased fibrinolytic activity. In this study, we generated PS-K196E and PLG-A622T (corresponding to human PLG-A620T) knock-in mice for investigating effects of these mutations in vivo. Following the induction of pulmonary embolism, PS-K196E mice showed increased degree of lung vascular occlusion and decreased survival compared with wild-type mice. These results support a direct causal relationship between the PS-K196E mutation and increased susceptibility to venous thromboembolism. To examine effects of the mutation on arterial ischemic diseases, temporary cerebral ischemia was applied in mice. Mice with the factor V－Leiden mutation, the common thrombotic risk in Caucasian, showed larger infarction and lower survival than wild-type mice. In contrast, cerebral infarction in PS-K196E mice was not aggravated. Consistent with these findings, the FV-Leiden mutation has been reported as a risk factor for early-onset ischemic stroke, whereas there are no epidemiological data to suggest significant association between the PS-K196E mutation and stroke. The PS-196E mice represent a suitable animal model to uncover genetic characteristics of thrombosis in Japanese. The PLG-A622T mutation in mice had little effect on the severity of pulmonary embolism and cerebral infarction, suggesting that the PLG-A620T mutation does not cause thrombosis by itself.
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Research Products
(26 results)
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[Journal Article] ADAMTS13 safeguards the myocardium in a mouse model of acute myocardial infarction2012
Author(s)
Doi M, Matsui H, Takeda Y, Saito Y, Takeda M, Matsunari Y, Nishio K, Shima M, Banno F, Akiyama M, Kokame K, Miyata T, Sugimoto M
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Journal Title
Thromb Haemost
Volume: 108
Pages: 1236-1238
DOI
Peer Reviewed
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[Journal Article] ADAMTS13 gene deletion enhances plasma high-mobility group box1 elevation and neuroinflammation in brain ischemia-reperfusion injury2012
Author(s)
Fujioka M, Nakano T, Hayakawa K, Irie K, Akitake Y, Sakamoto Y, Mishima K, Muroi C, Yonekawa Y, Banno F, Kokame K, Miyata T, Nishio K, Okuchi K, Iwasaki K, Fujiwara M, Siesjo BK
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Journal Title
Neurol Sci
Volume: 33
Pages: 1107-1115
DOI
Peer Reviewed
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[Journal Article] ADAMTS13 gene deletion aggravates ischemic brain damage : A possible neuroprotective role of ADAMTS13 by ameliorating post-ischemic hypoperfusion2010
Author(s)
Fujioka M, Hayakawa K, Mishima K, Kunizawa A, Irie K, Higuchi S, Nakano T, Muroi C, Fukushima H, Sugimoto M, Banno F, Kokame K, Miyata T, Fujiwara M, Okuchi K, Nishio K
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Journal Title
Blood
Volume: 115
Pages: 1650-1653
DOI
Peer Reviewed
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[Presentation] Protective role of ADAMTS13 for myocardium in mouse model of experimental myocardial infarction2012
Author(s)
Doi M, Matsui H, Takeda Y, Saito Y, Takeda M, Matsunari Y, Nishio K, Shima M, Banno F, Akiyama M, Kokame K, Miyata T, Sugimoto M
Organizer
54th ASH Annual Meeting and Exposition
Place of Presentation
Georgia World Congress Center, USA
Year and Date
2012-12-09
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[Presentation] ADAMTS13 improving the cell engraftment efficacy in mouse model of bone marrow transplantation2012
Author(s)
Matsui H, Doi M, Matsunari Y, Takeda M, Nishio K, Shima M, Soejima K, Banno F, Akiyama M, Kokame K, Miyata T, Sugimoto M
Organizer
54th ASH Annual Meeting and Exposition
Place of Presentation
Georgia World Congress Center, USA
Year and Date
2012-12-08
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