| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
We have reported that G201V mutation in PSMB8 gene encoding immunoproteasome beta 5i subunit causes an autoinflammatory disease, Nakajo-Nishimura syndrome (NNS) in 2011. In this study, we established NNS model mice harboring G201V mutation by gene-targeting method and analyzed their phenotypes. Excess accumulation of ubiquitinated proteins and excess nuclear translocation of phosphorylated p38 were observed in mice as in NNS patients, but homozygous mutant mouse didn’t develop NNS-like phenotypes. However, female homozygous mutant mice developed severe inflammations of the endocervix and fingers after parturition, and died within a month. Additionally, mutational analyses were performed for four Japanese families with unidentified autoinflammatory diseases. A de novo mutation was identified in a patient with an autoinflammatory disease using Next Generation Sequencing systems.
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