Develop and analysis for chromosome mutant mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Nomura Jun 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (70406528)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 自閉症 / 染色体操作 / 動物モデル / 統合失調症 / てんかん / 薬理

Outline of Final Research Achievements

In this term, we newly developed (chromosome mutant) animal models of autism spectrum disorder (ASD) for human 15q13.3 deletion, and GABAR cluster deletion in 15q11-q13 locus.
In particular, 15q13.3 model mice showed social deficits which mimic core symptom of patients with ASD. Simultaneously, we performed seizure assay as pharmacological test using animal model of 15q25.2-25.3 deletion and 15q13.3 deletion mice. In this analysis we applied non-liquid gas-system which efficiently cause seizure-like symptoms. In this assay, 15q13.3 heterozygote deletion mice didn't show clear changes, however, 15q13.3 homozugote mice increased frequency of generalized seizures. We also analyzed gender difference using 15q13.3 heterozygte and homozygote mice. However, no differences were observed in this assay. Thus, we concluded that 15q13.3 locus is associated with both ASD-like symptoms and seizure, but gender may not associated with these symptoms.

Free Research Field

精神神経科学，染色体工学

Academic Significance and Societal Importance of the Research Achievements

コミュニケーションの障害をコア症状とする自閉スペクトラム症は，単一遺伝子の変異とともに染色体レベルの欠失や重複でも相関が認められている．疾患の理解，創薬において動物モデルは必須であるが，染色体変異を反映したモデルは僅かである．このため本研究ではヒト染色体と相同性の高い15q25.2-25-3欠失モデルとともに，15q13.3欠失モデル，15q11-13内のGABA受容体のクラスターを欠失したモデルを新規で作製した．また自閉症患者ではてんかん発作も高頻度に認められるが，その関係を15q13.3モデルを用い解析したところ，当該染色体領域との有意な相関を認めた．