Production of full length alpha-actinin-3 protein from ACTN3 gene X genotype

• Project/Area Number: 16K13015
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Sports science
• Research Institution: The University of Tokushima
• Principal Investigator: HARADA Nagakatsu 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (40359914)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ACTN3 / alpha-actinin-3 / リードスルー / スポーツ / パワー・瞬発系 / R577X / 遺伝子多型 / アミノグリコシド系抗生物質 / リードスルー薬 / ゲンタマイシン / G418 / 運動適正 / X型 / R型 / α-actinin3 / 筋線維タイプ / 遺伝子 / 細胞・組織 / 栄養学

Outline of Final Research Achievements

A nonsense mutation of the ACTN3 gene generates a premature termination codon (PTC) and produces R/X polymorphism in humans. Since the X mRNA which contains a PTC is degraded by the cellular nonsense-mediated mRNA decay (NMD) system, ACTN3 XX genotype does not produce alpha-actinin-3 protein. Here we show that the readthrough drugs such as aminoglycosides could produce a full-length alpha-actinin-3 protein from the ACTN3 X gene.

Research Products

• [Journal Article] Endoplasmic reticulum stress in mice increases hepatic expression of genes carrying a premature termination codon via a nutritional status-independent GRP78-dependent mechanism. (2017)
  • Author(s): Harada N, Okuyama M, Yoshikatsu A, Yamamoto H, Ishiwata S, Hamada C, Hirose T, Shono M, Kuroda M, Tsutsumi R, Takeo J, Taketani Y, Nakaya I, Sakaue H.
  • Journal Title: J Cell Biochem Volume: 印刷中 Issue: 11 Pages: 3810-3824
  • DOI: 10.1002/jcb.26031
  • Peer Reviewed / Open Access
• [Journal Article] A novel lipoprotein (a) lowering drug, D-47, decreases neointima thickening after vascular injury (2017)
  • Author(s): Nakaya Y, Fukuda D, Oyamada T, Ogawa K, Harada N, Nakagami H, Morishita R, Sata M, Sakaue, H.
  • Journal Title: The Journal of Medical Investigation Volume: 64 Issue: 1.2 Pages: 64-67
  • DOI: 10.2152/jmi.64.64
  • NAID: 130005501982
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] Intracerebroventricular injection of ghrelin decreases wheel running activity in rats. (2016)
  • Author(s): Miyatake Y, Shiuchi T, Mawatari K, Toda S, Taniguchi Y, Futami A, Sato F, Kuroda M, Sebe M, Tsutsumi R, Harada N, Minokoshi Y, Kitamura T, Gotoh K, Ueno M, Nakaya Y, Sakaue H.
  • Journal Title: Peptide Volume: 87 Pages: 12-19
  • DOI: 10.1016/j.peptides.2016.11.005
  • Peer Reviewed / Open Access
• [Presentation] 魚油由来長鎖モノエン脂肪酸は抗動脈硬化作用を有する (2018)
  • Author(s): 丹波洋介，竹尾仁良，板東 正浩，瀬部真由，山崎幸，福田大受，宮原裕子，宮武由実子，末政直哉，黒田雅士，升本早枝子，原田永勝，堤理恵，佐田政隆，阪上浩
  • Organizer: 第21回日本病態栄養学会年次学術集会
• [Presentation] 自発運動がストレプトゾトシン誘発糖尿病モデルラットにおける筋萎縮に与える影響 (2017)
  • Author(s): 山崎幸，東千尋，堤理恵，竹治香菜，末政直哉，宮武由実子，原田永勝，阪上浩
  • Organizer: 第32回日本糖尿病合併症学会
• [Presentation] GADD34のC末端領域を欠損したCHO-K1細胞の樹立 (2016)
  • Author(s): 大塚 良，原田 永勝，水澤 典子，吉本 勝彦，西辻 和親，高石 和美，中屋 豊，阪上 浩，北畑 洋
  • Organizer: 第253回徳島医学会学術集会
  • Place of Presentation: 徳島県医師会館(徳島県徳島市）
  • Year and Date: 2016-07-24