• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Study of cerebellum disturbance by genetic approaches

Research Project

Project/Area Number 26242085
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic / Social brain science
Research InstitutionHiroshima University

Principal Investigator

Kawakami Hideshi  広島大学, 原爆放射線医科学研究所, 教授 (70253060)

Co-Investigator(Kenkyū-buntansha) 森野 豊之  広島大学, 原爆放射線医科学研究所, 准教授 (10397953)
大澤 亮介  広島大学, 原爆放射線医科学研究所, 助教 (20719356)
福士 雅也  広島大学, 医歯薬保健学研究科(医), 助教 (50313515)
山本 卓  広島大学, 理学研究科, 教授 (90244102)
丸山 博文  広島大学, 医歯薬保健学研究科(医), 教授 (90304443)
外丸 祐介  広島大学, 自然科学研究支援開発センター, 教授 (90309352)
平木 啓子  広島大学, 原爆放射線医科学研究所, 研究員 (10455397)
Project Period (FY) 2014-06-27 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥44,330,000 (Direct Cost: ¥34,100,000、Indirect Cost: ¥10,230,000)
Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2016: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2015: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2014: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Keywords脊髄小脳変性症 / Ca チャンネル / 脳神経疾患 / 遺伝子 / 神経科学 / 遺伝性脊髄小脳変性症
Outline of Final Research Achievements

We analyzed two Japanese families with autosomal dominant SCA using linkage analysis and exome sequencing, and identified CACNA1G, which encodes the calcium channel CaV3.1, as a new causative gene. Although most patients exhibited the pure form of cerebellar ataxia, two patients showed prominent resting tremor in addition to ataxia. CaV3.1 is classified as a low-threshold voltage-dependent calcium channel (T-type) . The mutation p.Arg1715His, identified in this study, was found to be located at S4 of repeat IV, the voltage sensor of the CaV3.1. Electrophysiological analyses revealed that the membrane potential dependency of the mutant CaV3.1 transfected into HEK293T cells shifted toward a positive potential
Our study also identifies Twinkle mutations as a cause of Perrault syndrome accompanied by neurologic features and expands the phenotypic spectrum of recessive disease caused by mutations in Twinkle.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (9 results)

All 2018 2017 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] First report of a Japanese family with spinocerebellar ataxia type 10: The second report from Asia after a report from China2017

    • Author(s)
      Naito Hiroyuki、Takahashi Tetsuya、Kamada Masaki、Morino Hiroyuki、Yoshino Hiroyo、Hattori Nobutaka、Maruyama Hirofumi、Kawakami Hideshi、Matsumoto Masayasu
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 5 Pages: 0177955-0177955

    • DOI

      10.1371/journal.pone.0177955

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PLK1-mediated phosphorylation of WDR62/MCPH2 ensures proper mitotic spindle orientation2017

    • Author(s)
      Miyamoto Tatsuo、Akutsu Silvia Natsuko、Fukumitsu Akihiro、Morino Hiroyuki、Masatsuna Yoshinori、Hosoba Kosuke、Kawakami Hideshi、Yamamoto Takashi、Shimizu Kenji、Ohashi Hirofumi、Matsuura Shinya
    • Journal Title

      Human Molecular Genetics

      Volume: 26 Issue: 22 Pages: 4429-4440

    • DOI

      10.1093/hmg/ddx330

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel compound heterozygous mutations in the PARK2 gene identified in a Chinese pedigree with early-onset Parkinson's disease2017

    • Author(s)
      Shi Yingying、Kawakami Hideshi、Zang Weizhou、Li Gang、Zhang Jiewen、Xu Changshui
    • Journal Title

      Brain and Behavior

      Volume: 8 Issue: 1

    • DOI

      10.1002/brb3.901

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vulnerability of Purkinje Cells Generated from Spinocerebellar Ataxia Type 6 Patient-Derived iPSCs.2016

    • Author(s)
      Ishida Y, Kawakami H, Kitajima H, Nishiyama A, Sasai Y, Inoue H, Muguruma K.
    • Journal Title

      Cell Rep

      Volume: 17 Issue: 6 Pages: 1482-1490

    • DOI

      10.1016/j.celrep.2016.10.026

    • NAID

      120006223645

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A mutation in the low voltage -gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia.2015

    • Author(s)
      Morino H., Matsuda Y., Muguruma K., Miyamoto R., Ohsawa R., Ohtake T., Otobe R., Watanabe M., Maruyama H., Hashimoto K., Kawakami H.
    • Journal Title

      Molecular Brain

      Volume: 8 Issue: 1 Pages: 1-9

    • DOI

      10.1186/s13041-015-0180-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.2015

    • Author(s)
      Muguruma K, et al.
    • Journal Title

      Cell Reports

      Volume: 10 Issue: 4 Pages: 537-550

    • DOI

      10.1016/j.celrep.2014.12.051

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features.2014

    • Author(s)
      Morino H
    • Journal Title

      Neurology

      Volume: 83 Issue: 22 Pages: 2054-2061

    • DOI

      10.1212/wnl.0000000000001036

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Perrault症候群の原因遺伝子C10orf2の変異によるmtDNA維持機構の障害2014

    • Author(s)
      森野豊之、川上秀史
    • Organizer
      日本人類遺伝学会第59回大会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-20 – 2014-11-23
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 伝子改変非ヒト動物及び脊髄小脳変性症の治療薬又は予防薬のスクリーニング法2018

    • Inventor(s)
      川上秀史、森野豊之、松田由喜子
    • Industrial Property Rights Holder
      広島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-031706
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2014-11-20   Modified: 2019-03-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi