|Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|Outline of Final Research Achievements
We found two Japanese families suffered from an autoinflammatory syndrome characterized by recurrent fever, nodular erythema and partial lipodystrophy (JASL) and identified a missense mutation in the immunoproteasome subunit PSMB8. The PSMB8 mutation caused autoinflammation through the dysfunction of immunoproteasome complexes, but the underlying molecular mechanism has not been clarified. To understand how dysfunction of immunoproteasomes causes autoinflammation, we established knock-in mouse harboring the same Psmb8 mutation as JASL patients and transgenic mice that expressed mutant Psmb8 under the invariant chain promoter. Both genetically modified young mice did not show any signs of inflammation and splenomegaly. The Psmb8 knock-in mice had a defect in adipocytes differentiation, which would be attributable to lipodystrophy phenotypes in JASL patients.