Establishment of new mental disease model mouse by heterochromatin factor HP1 deficiency

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07090
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kyoto University
• Principal Investigator: Yoshihara Toru 京都大学, 医学研究科, 特定助教 (00401935)
• Co-Investigator(Kenkyū-buntansha): 成瀬 智恵 京都大学, 医学研究科, 准教授 (30372486) ; 浅野 雅秀 京都大学, 医学研究科, 教授 (50251450)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: マウス / 精神疾患モデル / 行動解析 / エピジェネティクス

Outline of Final Research Achievements

Recently, failure of epigenetic regulatory mechanisms causes various mental disorders such as autism, bipolar disorder and depression. In this study, we focused on heterochromatin protein 1 (HP1), one of the histone modification factors. We tried to establish an HP1-deficient mouse as a new mental disorder model mouse and also applied to this gene deficient mouse to understand the relationships between epigenetic regulatory mechanism and pathogenesis. Based on the phenotypes related by comprehensive behavioral analysis, we found that this mouse has anxiety and depression-like behavioral traits. These behavioral traits were improved to almost the same level of control mice by drugs related to the dopaminergic nervous system, but not anti-anxiety drugs and antidepressants. Biochemical analysis also showed that the contents of monoaminergic neural transmitters, genes related to neural transmission system, exocytosis were not changed.

Free Research Field

行動神経科学

Academic Significance and Societal Importance of the Research Achievements

精神疾患を生じる危険因子として，遺伝子発現のエピジェネティック制御機構の破綻に注目が寄せられている．本研究ではヘテロクロマチンプロテイン1（HP1）と呼ばれる遺伝子に着目して，この遺伝子欠損マウスを作製した．このマウスの新たな精神疾患モデルマウスとしての妥当性と，このマウスを用いることで精神疾患の病因理解に新たな切り口をもたらすことを目的とした．その結果，この遺伝子欠損マウスは不安・うつ様の行動を持つこと，その行動障害はドーパミン神経系に作用する薬物によりコントロールマウスのレベルまで改善されることを見出すことができ，ドーパミン神経系障害に基づく精神疾患モデルになり得ることを示すことができた．