Investigation of neural circuits responsible for behavioral abnormalities caused by Dgcr8 deficiency

• Project/Area Number: 26460381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Research Institute, Shiga Medical Center
• Principal Investigator: Muraki Kazue 滋賀県立成人病センター(研究所), 神経病態研究部門, 主査 (10725857)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Dgcr8 / 22q11 deletion syndrome / schizophrenia / Cre / BAC / hippocampus / interneuron / dentate gyrus / miRNA / cortex / development / 22q11欠損症候群 / 介在神経細胞 / 統合失調症 / レンチウイルス

Outline of Final Research Achievements

22q11 deletion syndrome is a chromosome disorder. 20-30% of the patients with this deletion develop schizophrenia. We demonstrated the heterozygous deletion of Dgcr8 caused developmental abnormalities in the dentate gyrus of the hippocampus and cortical interneruons. To perform rescue experiments by Dgcr8 overexpression, we newly generated ROSA-CAG-stop-Dgcr8 BAC transgenic mice, which express Dgcr8 specifically in Cre-expressing cells.

Research Products

• [Int'l Joint Research] Johns Hopkins University(米国)
• [Journal Article] Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling. (2017)
  • Author(s): Toritsuka M, Kimoto S, Muraki K, Kitagawa M, Kishimoto T, Sawa A, Tanigaki K.
  • Journal Title: Transl Psychiatry. Volume: 7 Issue: 3 Pages: e1049-e1049
  • DOI: 10.1038/tp.2017.21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polymorphism within a Neuronal Activity-Dependent Enhancer of NgR1 Is Associated with Corpus Callosum Morphology in Humans (2015)
  • Author(s): Isobe M, Tanigaki K, Muraki K, Miyata J, Takemura A, Sugihara G, Takahashi H, Aso T, Fukuyama H, Hazama M, Murai T
  • Journal Title: Mol Neuropsychiatry Volume: 1 Issue: 2 Pages: 105-115
  • DOI: 10.1159/000430463
  • Peer Reviewed
• [Journal Article] Arsenic trioxide sensitizes glioblastoma to a myc inhibitor. (2015)
  • Author(s): Yoshimura Y, Shiino A, Muraki K, Fukami T, Yamada S, Satow T, Fukuda M, Saiki M, Hojo M, Miyamoto S, Onishi N, Saya H, Inubushi T, Nozaki K, Tanigaki.
  • Journal Title: Plos One Volume: 10 Issue: 6 Pages: e0128288-e0128288
  • DOI: 10.1371/journal.pone.0128288
  • NAID: 120005947136
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal migration abnormalities and its possible implications for schizophrenia. (2015)
  • Author(s): Kazue Muraki, Kenji Tanigaki
  • Journal Title: Front Neurosci. Volume: 9 Pages: 74-74
  • DOI: 10.3389/fnins.2015.00074
  • Peer Reviewed / Open Access