Functional analysis of genes responsible for neurological diseases by conditional mutagenesis in a single generation

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K01972
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Niigata University
• Principal Investigator: Abe Manabu 新潟大学, 脳研究所, 准教授 (10334674)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: 神経疾患原因遺伝子 / ゲノム編集 / コンディショナル遺伝子発現制御

Outline of Final Research Achievements

In this project, I attempted to develop a novel method for the regulation of conditional gene expression using the FLEx system and genomes derived from different species. A total of six knock-in mouse strains were established using the novel method. We also developed a method of producing genetically engineered mice. In the genome editing of early mouse embryos using the electroporation method, we were able to establish a technology that enables the knock-in of longer sequences more easily. One of the objectives of this study is to elucidate some aspects of the molecular mechanisms of cerebellar development, focusing on two genes that cause neurological diseases, Car8, Eef1a2, and their related molecules. Although we did not obtain much information on the molecular mechanism of cerebellar development, we believe that we were able to achieve remarkable results in terms of the regulation of gene expression and the development of technology for producing genetically modified mice.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究においてゲノム編集による遺伝子改変動物作製について技術的にさらに向上させたことで多くの生命科学研究の推進に寄与することができると期待され、また、遺伝子発現制御法の改良は遺伝子機能の評価をより正確にするという点で学術的意義は高い。さらに、一系統のマウスを希少神経疾患であるTimothy症候群の病態モデルとして研究代表者が発明者の一人となり特許出願したことから、本研究成果を社会へ還元できる可能性も高い。