Genetic analysis and establishment of in vitro model for inclusion body myositis

• Project/Area Number: 26670436
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Aoki Masashi 東北大学, 医学(系)研究科(研究院), 教授 (70302148)
• Co-Investigator(Kenkyū-buntansha): Kato MASAAKI 東北大学, 病院, 助教 (50622479) ; SUZUKI Naoki 東北大学, 病院, 助教 (70451599) ; WARITA Hitoshi 東北大学, 大学院医学系研究科, 助教 (30400245)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 封入体筋炎 / 骨格筋 / プロテアソーム

Outline of Final Research Achievements

Sporadic inclusion body myositis (sIBM) is an intractable and progressive skeletal muscle disease of unknown etiology and without effective treatment. Muscle biopsy typically reveals endomysial inflammation, invasion of mononuclear cells into non-necrotic fibers and rimmed vacuoles, suggesting inflammation and degeneration co-exist as part of the pathomechanism. We made muscle specific proteasomal deficient mice and reported in JCS paper. We also found familial case of inclusion body myopathy with the mutation in hnRNPA1. We also established iPS cells from these patients.

Research Products

• [Journal Article] A mutation in hnRNPA1 causes isolated inclusion body myopathy in two families with multisystem proteinopathy (2015)
  • Author(s): Izumi R, Warita H, Niihori T, Takahashi T, Tateyama M, Suzuki N, Nishiyama A, Shirota M, Funayama R, Nakayama K, Mitsuhashi S, Nishino I, Aoki Y, Aoki M.
  • Journal Title: Neurology Genetics Volume: NA
  • Peer Reviewed / Open Access
• [Journal Article] Proteasome dysfunction induces muscle growth defects and protein aggregation (2014)
  • Author(s): Kitajima Y, Tashiro Y, Suzuki N, Warita H, Kato M, Tateyama M, Ando R, Izumi R, Yamazaki M, Abe M, Sakimura K, Ito H, Urushitani M, Nagatomi R, Takahashi R, and Aoki M
  • Journal Title: J Cell Sci Volume: 127 Pages: 5204-5217
  • DOI: 10.1242/jcs.150961
  • Peer Reviewed / Open Access