Developmentandapplicationofmouseandcellmodelsforanalyses of HLA-dependent adverse drug reactions

2014 Fiscal Year Final Research Report

• Project/Area Number: 24700435
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Tokai University
• Principal Investigator: MIURA Hiromi 東海大学, 医学部, 特定研究員 (90599523)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: トランスジェニックマウス / 薬剤副作用 / HLA / 肝障害

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.

Free Research Field

遺伝子工学・実験動物学