Generation of locomotive syndrome model

• Project/Area Number: 15K14373
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Aoyama Gakuin University
• Principal Investigator: Hirata Hiromi 青山学院大学, 理工学部, 教授 (60402450)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝子 / 遺伝学 / 筋

Outline of Final Research Achievements

Aging problem is a series issue In Japan and the word "locomo" is drawing public attention. It is the abbreviation of locomotive syndrome, which is a condition of reduced mobility due to impairment of motor organs such as muscle, joint and bone. To developed a pathophysiological model of locomotive syndrome, we generated transgenic zebrafish expressing nuclear-localizing GFP, plasmamembrane-localizing YFP and filamentous actin-binding RFP in muscle cells. By crossing these lines, we have developed triple transgenic expressing these three fluorescent proteins in the same animals, enabling the visualization of nucleus, plasmamembrane and F-actin in live animals for quantitative analysis. Since studies of natural aging take time, we tried to develop fish models of progeria. Using CRISPR/Cas9 method, we generated several deletion alleles of aging-related genes in zebrafish. By crossing muscle imaging line and progeria model line, we are developing a new tool for locomotive syndrome study.

Research Products

• [Journal Article] Activation-dependent rapid postsynaptic clustering of glycine receptors in mature spinal cord neurons. (2017)
  • Author(s): Nakahata, Y., Eto, K., Murakoshi, H., Watanabe, M., Kuriu, T., Hirata, H., Moorhouse, A. J., Ishibashi, H. and Nabekura, J.
  • Journal Title: eNeuro Volume: 4 Pages: 1-20
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mutations in subunits of the activating signal cointegrator 1 complex are associated with prenatal spinal muscular atrophy and congenital bone fractures. (2016)
  • Author(s): Knierim, E., Hirata, H., Wolf, N. I., Morales-Gonzalez, S., Schottmann, G., Tanaka, Y., Rudnick-Schoneborn, S., Orgeur, M., Zerres, K., Vogt, S., van Riesen, A., Gill, E., Seifert, F., Zwirner, A., Kirschner, J., Goebel, H. H., Hubner, C., Stricker, S., Meierhofer, D., Stenzel, W. and Schuelke, M.
  • Journal Title: Am. J. Hum. Genet. Volume: 98 Pages: 473-489
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Defects of the glycinergic synaptic in zebrafish. (2016)
  • Author(s): Ogino, H. and Hirata, H.
  • Journal Title: Front. Mol. Neurosci. Volume: 9 Pages: 1-18
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Loss of ift122, a retrograde intrafragellar transport (IFT) complex component, leads to slow, progressive photoreceptor degeneration due to inefficient opsin transport. (2016)
  • Author(s): Boubakri, M., Chaya, T., Hirata, H., Kajimura, N., Kuwahara, R., Ueno, A., Malicki, J., Furukawa, T. and Omori, Y.
  • Journal Title: J. Biol. Chem. Volume: 291 Pages: 24465-24474
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] RING finger protein 121 facilitates the degradation and membrane localization of voltage-gated sodium channels (2015)
  • Author(s): Ogino, K., Low, S.E., Yamada, K., Saint-Amant, L., Zhou, W., Muto, A., Asakawa, K., Nakai, J., Kawakami, K., Kuwada, J.Y., and Hirata, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 112 Issue: 9 Pages: 2859-2864
  • DOI: 10.1073/pnas.1414002112
  • Peer Reviewed
• [Journal Article] Neuromuscular regulation in zebrafish by a large AAA+ ATPase/ubiquitin ligase, mysterin/RNF213. (2015)
  • Author(s): Kotani Y, Morito D, Yamazaki S, Ogino K, Kawakami K, Takashima S, Hirata H, Nagata K.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 16161-16161
  • DOI: 10.1038/srep16161
  • Peer Reviewed / Open Access
• [Journal Article] Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures. (2015)
  • Author(s): Stödberg, T., McTague, A., Ruiz, A. J., Hirata, H. et al.
  • Journal Title: Nat. Commun. Volume: 6 Issue: 1 Pages: 8038-8038
  • DOI: 10.1038/ncomms9038
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] ゼブラフィッシュを用いた骨格筋細胞の解析 (2016)
  • Author(s): 平田普三
  • Organizer: 第4回若手による骨格筋細胞研究会
  • Place of Presentation: ウィンクあいち（名古屋）
  • Year and Date: 2016-11-14
• [Presentation] 脳疾患、脊髄変性疾患、筋疾患のゼブラフィッシュモデル (2016)
  • Author(s): 平田普三
  • Organizer: 第2回ゼブラフィッシュ創薬研究会
  • Place of Presentation: みんなの森ぎふメディアコスモス（岐阜）
  • Year and Date: 2016-11-04
• [Presentation] ゼブラフィッシュを用いた運動器の遺伝学的解析 (2016)
  • Author(s): 平田普三
  • Organizer: 第4回骨格筋生物学研究会
  • Place of Presentation: 松本大学（松本）
  • Year and Date: 2016-03-05
• [Presentation] Plasticity of glycinergic synapses and related behaviors in zebrafish. (2015)
  • Author(s): Hirata, H.
  • Organizer: The 25th meeting of the International Society for Neurochemistry.
  • Place of Presentation: Cairns Convention Center. Cairns, Australia.
  • Year and Date: 2015-08-24
  • Int'l Joint Research / Invited
• [Presentation] 電位依存性ナトリウムチャネルの輸送におけるGPIアンカータンパク生合成の重要性 (2015)
  • Author(s): 平田普三
  • Organizer: 第34回日本糖質学会年会
  • Place of Presentation: 東京大学安田講堂（東京）
  • Year and Date: 2015-08-02
  • Invited