Elucidation the pathomechanisms of conformational diseases through analyzing the model mice of sporadic inclusion myositis
| Project/Area Number |
26860674
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Kumamoto University |
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Principal Investigator |
Tawara Akie 熊本大学, 医学部附属病院, 医員 (00726333)
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| Research Collaborator |
ANDO Yukio
YAMASHITA Satoshi
TAWARA Nozomu
Doki Tsukasa
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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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| Keywords | 孤発性封入体筋炎 / TDP-43 / LC-MS/MS / NT5C1A / 封入体筋炎 / プロテオミクス解析 |
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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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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Clinicopathological features of the first Asian family having vocal cord and pharyngeal weakness with distal myopathy due to a MATR3 mutation.2015
Author(s)
Yamashita S, Mori A, Nishida Y, Kurisaki R, Tawara N, Nishikami T, Misumi Y, Ueyama H, Imamura S, Higuchi Y, Hashiguchi A, Higuchi I, Morishita S, Yoshimura J, Uchino M, Takashima H, Tsuji S, Ando Y.
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Journal Title
Neuropathol Appl Neurobiol
Volume: 41
Issue: 3
Pages: 391-398
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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