Analysis of Dicc-M KO mice to reveal the pathogenesis of schizophrenia

• Project/Area Number: 21591535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: OHNISHI Tetsuo 独立行政法人理化学研究所, 分子精神科学研究チーム, 研究員 (80373281)
• Co-Investigator(Kenkyū-buntansha): YOSHIKAWA Takeo 独立行政法人理化学研究所, 分子精神科学研究チーム, チームリーダー (30249958)
• Co-Investigator(Renkei-kenkyūsha): ITOKAWA Masanari (財)東京都医学研究機構, 東京都精神医学総合研究所, 副参事研究員 (40332324) ; ARAI Makoto (財)東京都医学研究機構, 東京都精神医学総合研究所, 研究員 (80356253)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 統合失調症 / ノックアウトマウス / 行動実験 / DISC1 / 転写因子 / 染色体転座 / ドーパミン / グルタミン酸 / マイクロアレイ / MK801 / methylphenidate / amphetamine / Ldb2 / 染色体異常 / モデルマウス / 扁桃体 / 恐怖条件付け

Research Abstract

In this study, we have focused on the schizophrenia-relevant gene DISC1, which is disrupted by a chromosomal break seen in a Japanese schizophrenic patient. Because the function of this gene remains totally unknown, we first set out to examine the phenotype of Disc-M KO mice. The KO mice exhibited multiple deficits relevant to schizophrenia : hyperacticity in the drug-naive mice, hypersensitivity to NMDA antagonist and DA agonist. Interestingly, cued fear conditioning was totally damaged by disruption of the Disc-M gene. These data may reflect that disruption of the gene by the chromosomal break this gene is really pathogenic at least in the proband.

Research Products

• [Journal Article] Ablation of Mrds1/Ofcc1 induces hyper-γ-glutamyl transpeptidasemia without abnormal head development and schizophrenia-relevant behaviors in mice (2011)
  • Author(s): Ohnishi T, Yamada K, Watanabe A, Ohba H, Sakaguchi T, Honma Y, Iwayama Y, Toyota T, Maekawa M, Watanabe K, Detera-Wadleigh SD, Wakana S, Yoshikawa T
  • Journal Title: PLoS One Volume: 6(12)
  • Peer Reviewed
• [Journal Article] Analysis of strain-dependent prepulse inhibition points to a role for Shmt1(SHMT1) in mice and in schizophrenia (2010)
  • Author(s): Maekawa M, Ohnishi T, Hashimoto K, Watanabe A, Iwayama Y, Ohba H, Hattori E, Yamada K, Yoshikawa T
  • Journal Title: J Neurochem Volume: 115(6) Pages: 1374-85
  • Peer Reviewed
• [Journal Article] Enhanced carbonyl stress in a subpopulation of schizophrenia (2010)
  • Author(s): Arai M, Yuzawa H, Nohara I, Ohnishi T, Obata N, Iwayama Y, Haga S, Toyota T, Ujike H, Arai M, Ichikawa T, Nishida A, Tanaka Y, Furukawa A, Aikawa Y, Kuroda O, Niizato K, Izawa R, Nakamura K, Mori N, Matsuzawa D, Hashimoto K, Iyo M, Sora I, Matsushita M, Okazaki Y, Yoshikawa T, Miyata T, Itokawa M
  • Journal Title: Arch Gen Psychiatry Volume: 67(6) Pages: 589-97
  • NAID: 130005395360
  • Peer Reviewed
• [Journal Article] Enhanced Carbonyl Stress in a Subpopulation of Schizophrenia (2010)
  • Author(s): Arai, Yuzawa, Nohara, Ohnishi, et al.
  • Journal Title: Arch Gen Psych Volume: 67 Pages: 589-597
  • NAID: 130005395360
  • Peer Reviewed
• [Journal Article] Behavioral analyses of transgenic mice harboring bipolar disorder candidate genes, IMPA1 and IMPA2 (2010)
  • Author(s): Ohnishi, et al.
  • Journal Title: Reuroscience Research Volume: 67 Pages: 86-94
  • Peer Reviewed
• [Journal Article] Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SBMT1) in mice and in schizophrenia. (2010)
  • Author(s): Maekawa, Ohnishi, et al.
  • Journal Title: J Neurochem Volume: 115 Pages: 1374-1385
  • Peer Reviewed
• [Presentation] Mice deficient in a gene encoding a transcriptional regulator exhibit multiple behavioral deficits reminiscent of schizophrenia (2011)
  • Author(s): Ohnishi T, Watanabe A, M. Arai, Itokawa M, Yoshikawa T, et al
  • Organizer: 66th Annual Meeting, Society for Biological Psychiatry
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-05-14
• [Presentation] Mice deficient in a gene encoding a transcriptional regulator exhibit multiple behavioral deficits reminiscent of schizophrenia (2011)
  • Author(s): T Ohnishi, et al
  • Organizer: 66th Annual Convention, Society of Biological Psychiatry
  • Place of Presentation: Hotel Hilton SF, San Francisco, USA
  • Year and Date: 2011-05-14
• [Presentation] 精神疾患の生物学的研究 (2010)
  • Author(s): 大西哲生
  • Organizer: 東京都精神医学総合研究所セミナー
  • Place of Presentation: 東京
  • Year and Date: 2010-11-29
• [Book] 第三章脳神経系:精神疾患 (2011)
  • Author(s): 大西哲生、吉川武男
  • Publisher: 中山書店
• [Book] 論文ができてしまう!疾患モデルマウス表現型解析指南(編集・山村研一、若菜茂晴) (2011)
  • Author(s): 大西哲生、吉川武男(分担)
  • Publisher: 中山書店
• [Book] 疾患モデルマウスと表現型解析～これだけ調べれば論文が書ける～ (2011)
  • Author(s): 大西哲生、吉川武男
  • Total Pages: 5
  • Publisher: 中山書店(印刷中)