Modelling psychiatric disorders with iPS technology and genetically engineered mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02574
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Tokyo University of Agriculture (2020); Osaka University (2018-2019)
• Principal Investigator: Nakazawa Takanobu 東京農業大学, 生命科学部, 教授 (00447335)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: iPS細胞 / トランスレーショナル研究 / 統合失調症 / 自閉スペクトラム症 / ゲノムコピー数変異 / de novo突然変異

Outline of Final Research Achievements

In mice models of psychiatric disorders with POGZ Q1042R mutation or 3q29 deletion, both of which are expected to be strongly associated with psychiatric disorders, we found psychiatric disorder-related behavioral abnormalities, including impaired prepulse inhibition, impaired social behavior, repetitive and persistent behaviors and abnormal ultrasonic vocalization. We also found the neural activity in the anterior cingulate cortex in the POGZ mutant mice and the auditory cortex in the mice with 3q29 deletion were abnormally activated. Importantly, we found that the social behavioral abnormalities in the POGZ mutant mice and mice with 3q29 deletion can be recovered pharmacologically even in the adult stages. These results are useful not only for clarifying the molecular pathogenesis of the disease, but also for providing fundamental biological information for drug discovery research.

Free Research Field

分子神経科学

Academic Significance and Societal Importance of the Research Achievements

精神疾患分野では、患者に共通した疾患関連遺伝子を同定することができておらず、発症や病態の分子機序がいまだ不明である。従って、患者に共通する変異のみならず、病態に直結することが期待される効果サイズが大きい変異を持つ患者を地道に解析することが重要である。POGZ変異や3q29領域欠失は、その頻度は稀であるものの、疾患との関連性が強く示唆されており、本研究で得られた成果は、精神疾患の分子病態の解明に貢献するのみならず、創薬研究ための基礎データを提供するものである。