Developmentandapplicationofmouseandcellmodelsforanalyses of HLA-dependent adverse drug reactions
| Project/Area Number |
24700435
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Laboratory animal science
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| Research Institution | Tokai University |
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Principal Investigator |
MIURA Hiromi 東海大学, 医学部, 特定研究員 (90599523)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | トランスジェニックマウス / 薬剤副作用 / HLA / 肝障害 / PITT法 / トランスジェックマウス作製 / HLA発現確認 / トランスジェックマウス |
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| Outline of Final Research Achievements |
Recently, it has been revealed that adverse drug reaction is highly associated with specific HLA alleles. However, its pathogenic mechanism has still not been elucidated and the resources such as HLA-expressing cell lines and mice remained to be developed. This study established systems for high-throughput generation of cell and mouse resources suitable for analyses of HLA-dependent adverse drug reactions. Utilizing original vector and piggyBac transposon system, several cell lines each expressing HLA-A*33:03, A*31:01, B*15:02, and B*58:01 were established. The resultant cell lines exhibited high and stable expression of HLA. We also generated HLA class I transgenic (Tg) mice with pronuclear injection-based targeted transgenesis (PITT) method established in our laboratory. By using cloning vector developed by BAC modification, we generated HLA-A*33:03 and HLA-A*31:01 Tg mice. The experiments addressing pathogenic mechanism of HLA-related adverse drug reactions are currently underway.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] One-step generation of multiple transgenic mouse lines using an improved Pronuclear Injection-based Targeted Transgenesis (i-PITT)2015
Author(s)
Ohtsuka M., Miura H., Mochida K., Hirose M., Hasegawa A., Ogura A., Mizutani R., Kimura M., Isotani A., Ikawa M., Sato M. and Gurumurthy C. B.
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Journal Title
BMC Genomics
Volume: 16
Issue: 1
Pages: 274-274
DOI
NAID
Related Report
Peer Reviewed / Open Access
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