Elucidation the pathomechanisms of conformational diseases through analyzing the model mice of sporadic inclusion myositis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860674
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: Tawara Akie 熊本大学, 医学部附属病院, 医員 (00726333)
• Research Collaborator: ANDO Yukio ; YAMASHITA Satoshi ; TAWARA Nozomu ; Doki Tsukasa
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 孤発性封入体筋炎 / TDP-43 / LC-MS/MS / NT5C1A

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.

Free Research Field

神経内科