Generation of neurodegenerative disease model macaques

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K14578
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Hitoshi Seiji 滋賀医科大学, 医学部, 教授 (70300895)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: カニクイザル / 神経変性疾患 / アルツハイマー病 / 筋萎縮性側索硬化症

Outline of Final Research Achievements

We have established the lentivirus-mediated gene transfer technology and generated Alzheimer’s disease model macaques, which express mutated human APP gene. We have also developed several reagents, with which amyloid deposition in the macaque brain is visualized by MRI, and a touch panel-based behavior analysis device. In addition, we have constructed lentivirus expressing mutated FUS gene, one of causative genes of familial amyotrophic lateral sclerosis, under the control of inducible tetracycline system. After the infection of this lentivirus, neurons derived from crab-eating monkey ES cells expressed mutated FUS, which located in the cytoplasm but not in the nucleus and formed aggregates. Using this lentivirus, we observed mutated FUS was introduced to fertilized eggs of crab-eating monkeys.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患の動物モデルとして、様々な遺伝子改変マウスが開発されてきたが、脳のサイズや構造的類似性、高度な機能などの面から、霊長類疾患モデルの有用性は高い。本研究は、アルツハイマー病や筋萎縮性側索硬化症をターゲットに、患者で報告されている遺伝子変異をカニクイザルに導入し、神経細胞における早期の病変の検出を試みた。これらの神経変性疾患デルザル作製により、疾患病態の理解が深められることに加え、新たな治療薬が考案された場合に、前臨床試験に用いることができ、新規治療薬開発や安全性の確保に大きな意義があると考えられる。