| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Sporadic inclusion body myositis (sIBM) demonstrates inflammatory findings and degenerative features. Recently, TAR DNA-binding protein of 43 kDa (TDP-43) has been reported to be accumulated within degenerative myofibers of sIBM. At this point, it remained unclear whether the sarcoplasmic accumulation of TDP-43 is a primary trigger of muscle degeneration. The aim of our study is to dissolve whether muscle-dominant overexpression of TDP-43 can primarily cause muscle degeneration. We generated mice with muscle-dominant TDP-43 expression, and analyzed the phenotypes using biochemical, histological, and proteomic techniques including laser microdissection with LC-MS/MS. TDP-43 transgenic mice showed increased levels of CK. Myopathology demonstrated vacuolar formation and aggregation of TDP-43. Proteomic analysis using aggregated materials in degenerative myofibers identified increased levels of chaperons recognizing misfiled proteins. TDP-43 expression indeed caused myofiber degeneration.
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