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SHANK3変異マカクの異常な行動と接続性
Yang Zhou1,2,3, Jitendra Sharma4,5,6,7, Qiong Ke8,9
1Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Nature
|June 14, 2019
まとめ
研究者はCRISPR-Cas9を用いてマカクのSHANK3遺伝子変異を生成した. これらの遺伝子編集されたマカクは 自閉症スペクトル障害のような行動と 神経の変化を示し 障害を研究し 治療法を開発するための有望なモデルを提供します
科学分野:
- 神経科学
- 遺伝学
- 発達生物学
背景:
- SHANK3遺伝子の変異は,自閉症スペクトル障害 (ASD) とフェラン-マクダーミッド症候群の主要な遺伝的リスク因子です.
- 非人間霊長類のモデルは,ASDの表型と治療法を研究するために,ネズミのモデルよりも潜在的な利点を提供しています.
研究 の 目的:
- CRISPR-Cas9遺伝子編集を使用して,SHANK3欠乏症の非ヒト霊長類モデルを生成し,特徴づけること.
- シノモルガス・マカクのSHANK3変異の 神経と行動の影響を調査する
主な方法:
- CRISPR-Cas9遺伝子の編集は,シノモルガス・マカックの生殖線に感染するSHANK3変異を生成するために使用された.
- ゲノタイプ,タンパク質分析,機能磁気共鳴画像 (fMRI) および行動評価が行われました.
主要な成果:
- SHANK3の変異は体細胞と脳組織で確認され,SHANK3のタンパク質濃度が低下しました.
- fMRIでは 脳の接続パターンが変化して 回路の異常を示しています
- 変異したマカケイは 睡眠障害,運動障害,繰り返しの行動,社会や学習障害を示しました
結論:
- マカクのCRISPR-Cas9媒介のSHANK3変異はASDとフェラン-マクダーミッド症候群の関連モデルを成功裏に生成した.
- この霊長類のモデルは これらの状態の 重要な遺伝的,神経的,行動的特徴を 再現しています
- このモデルは,SHANK3に関連した神経発達障害の理解と治療を進めるために有望です.
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