| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
The mutation in PSMB8 causes autoinflammation and lipodystrophy due to low activity of immunoproteasomes in human. The molecular basis of these symptoms, however, remains undetermined. We established a mouse that harbors a mutation in Psmb8 (Psmb8-KI mouse) in order to analyze the molecular mechanisms of various symptoms in patients with a mutation in PSMB8.
Psmb8-KI mouse exhibits increased sensitivity for imiquimod-induced dermatitis. The dermatitis in Pmsb8-KI and wild type mouse was suppressed by the inhibition of inflammatory cytokines but neither inhibition was effective to cancel the increased sensitivity in Psmb8-KI mouse. I found that the ear of IMQ-treated KI mice expressed higher X gene expression than wild type mice. The inhibitor of X-related pathway treatment suppressed the increased swelling of the ear observed in Psmb8-KI mice.
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