Comprehensive analysis for animal model of chromosome rearrangement

• Project/Area Number: 26870397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology; Psychiatric science
• Research Institution: Hiroshima University
• Principal Investigator: Nomura Jun 広島大学, 医歯薬保健学研究院, 特任助教 (70406528)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 染色体工学 / 精神疾患 / 疾患モデル / 発達障害 / ジーンターゲティング / 自閉症 / ES細胞 / ゲノム編集

Outline of Final Research Achievements

Recently, large scale genomic database revealed that 15q25.2-25.3 as a one of the novel risk loci for developmental disorders. Indeed three patients with 15q25.2-25.3 deletion exhibited autistic or neurological phenotypes indicating that this locus may involved in psychological/emotional aspects. To analyze association between this risk locus and behavioral abnormalities, we developed humanized mice model which recapitulate human 15q25.2-25.3 deletion by using chromosome engineering technique. In this term, first, we transferred mouse genetic background, 129 to C57BL/6J, to conduct behavioral neuroscience research. The speed congenic method enable us to start next study earlier than expected but spent one year. Next, we conducted comprehensive behavioral analysis to identify risk loci related behavioral abnormalities. Although typical autistic behaviors (e.g. social deficit and repetitive behavior) have not seen in this mouse, anxiety related behaviors were observed.

Research Products

• [Journal Article] Role for neonatal D-serine signaling: prevention of physiological and bahavioral deficits in adult Pick1 knockout mice (2016)
  • Author(s): Nomura J, Jaaro-Peled H, Lewis E, Nunez-Abades P, Huppe-Gourgues F, Cash-Padgett T, Emiliani F, Kondo MA, Furuya A, Landek-Salgado MA, Ayhan Y, Kamiya A, Takumi T, Huganir R, Pletnikov M, O'Donnell P, Sawa A
  • Journal Title: Mol Psychiatry Volume: 21 Issue: 3 Pages: 386-393
  • DOI: 10.1038/mp.2015.61
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Involvement of Serotonin Transporter Gene Polymorphisms (5-HTT) in Impulsive Behavior in the Japanese Population (2015)
  • Author(s): NOMURA, M., KANEKO, M., OKUMA, Y., NOMURA, J., KUSUMI, I., KOYAMA, T., NOMURA, Y
  • Journal Title: PLoS One Volume: 16 Issue: 3 Pages: 1-14
  • DOI: 10.1371/journal.pone.0119743
  • NAID: 120005745671
  • Peer Reviewed / Open Access
• [Presentation] 発達期における D- セリンの役割：Pick1 ノックアウトマウスをモデルとして (2015)
  • Author(s): Nomura J, Jaaro-Peled H, Lewis E, Nunez-Abades P, Huppe-Gourgues F, Cash-Padgett T, Emiliani F, Kondo MA, Furuya A, Landek-Salgado MA, Ayhan Y, Kamiya A, Takumi T, Huganir R, Pletnikov M, O'Donnell P, Sawa A.
  • Organizer: 第45回日本神経精神薬理学会・第37回日本生物学的精神医学会合同年会
  • Place of Presentation: 東京（タワーホール船堀）
  • Year and Date: 2015-09-24
• [Presentation] ゲノム編集技術による簡便迅速かつ高効率な次世代染色体工学の開発 (2014)
  • Author(s): 野村 淳, 佐久間 哲史, 神田 暁史, 岸本 恵子, 前田 知花, 外丸 祐介, 山本 卓, 内匠 透
  • Organizer: 第37回分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] ゲノム編集技術による簡便迅速かつ高効率な次世代染色体工学の開発 (2014)
  • Author(s): 野村 淳, 佐久間 哲史, 神田 暁史, 岸本 恵子, 前田 知花, 外丸 祐介, 山本 卓, 内匠 透
  • Organizer: 第4回ゲノム編集研究会
  • Place of Presentation: 広島
  • Year and Date: 2014-10-06 – 2014-10-07