| 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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| 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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