Examination of involvement of vesicle transport mechanism in neurodegenerative disease using tissue specific gene deletion method

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Nara Women's University
• Principal Investigator: Watanabe Toshio 奈良女子大学, 自然科学系, 教授 (60201208)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 小胞輸送 / ARF / 神経特異的欠損 / 細胞増殖遅延 / BMPシグナル亢進

Outline of Final Research Achievements

A mouse lacking Arf1 only in neurons dies shortly after weaning with movement disorder of the hind limbs. We clarified the decrease in the number of granule cells in the cerebellum. We succeeded in creating a Fucci-expressing cell line capable of analyzing the doubling time and cell cycle in Arf1-deficient MEF cells. When tissue-specific deletion of Arf 1 and/or 6 in T and B lymphocytes were induced, abnormalities in the immune mechanism (such as abnormal maturation and abnormal antibody secretion) were found. We succeeded in generating mice for the preparation of Arf1 & 6 double-deficient MEF cells. In the SMAP1 & 2 double-deficient cells, we found that the signal loss is specifically delayed in the activity of the BMP signal (duration of the activity).

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果によって、「神経変性疾患を小胞輸送異常が引き起こす疾患」として捉えすことの妥当性が、小胞形成開始因子として細胞で良く解析されてきたArf1を用いてマウス個体レベルで示されたことは学術的に大きな意義がある。逆を考えれば、Arf1の活性化薬剤は神経変性疾患の予防や治療に応用できるかもしれないという社会的な意義も求められる。さらに、免疫をつかさどるT細胞、B細胞でのArf1の重要性を発見したことは、免疫系における新しいArf1機能の解明を期待させ、学術的にも社会的にも意義がある。