Abnormal transcriptional regulation in Cockayne syndrome and its effect on neuronal differentiation

• Project/Area Number: 15K06758
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: The University of Tokushima (2016-2017); Oita University (2015)
• Principal Investigator: HASHIMOTO Satoru 徳島大学, 病院, 特任講師 (60352150)
• Co-Investigator(Kenkyū-buntansha): 花田 克浩 大分大学, 医学部, 助教 (90581009) ; 高成 広起 徳島大学, 病院, 特任講師 (70723253) ; 寺林 健 大分大学, 医学部, 助教 (40452429)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: コケイン症候群

Outline of Final Research Achievements

Cockayne syndrome is a rare autosomal recessive disease with a mutation on DNA repair genes against UV induced DNA lesions. Since Cockayne syndrome has multiple phenotypes, the pathophysiological symptoms of Cockayne syndrome patients are rather complicated. To explore the new function of Cockayne synfrome genes, we investigated the cell-differentiation experiments using SH-SY5Y cells. We success to established mild and severe Cockayne syndrome model cells using CRISPR system against CSB gene, and found the difference between mild and severe model cells upon cell differentiation inducing factors.

Research Products

• [Int'l Joint Research] IGBMC(France)
• [Journal Article] MED12-related XLID disorders are dose-dependent of immediate early genes (IEGs) expression (2017)
  • Author(s): Donnio LM, Bidon B, Hashimoto S, May M, Epantchintsev A, Ryan C, Allen W, Hackett A, Gecz J, Skinner C, Stevenson RE, de Brouwer AP, Coutton C, Francannet C, Jouk PS, Schwartz CE, Egly JM
  • Journal Title: Human Molecular Genetics Volume: 印刷中 Pages: 2062-2075
  • DOI: 10.1093/hmg/ddx099
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Mechanisms of interstrand DNA crosslink repair and human disorders (2016)
  • Author(s): Hashimoto S, Anai H, Hanada K
  • Journal Title: Genes and Environment Volume: 38 Pages: 1-8
  • DOI: 10.1186/s41021-016-0037-9
  • Peer Reviewed / Open Access / Acknowledgement Compliant