Genetic analysis of host erythrocyte factor on proliferation of malaria parasite

Research Project

Project/Area Number	17K07134
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Laboratory animal science
Research Institution	Nagoya University
Principal Investigator	Ohno Tamio 名古屋大学, 医学系研究科, 准教授 (90293620)
Project Period (FY)	2017-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	ゲノム編集 / 赤血球 / 原虫増殖抑制遺伝子 / ネズミマラリア原虫 / マウス / マラリア原虫 / CRISPR/Cas9システム
Outline of Final Research Achievements	It was well known that the Char1/Pymr locus located on chromosome 9 is the major locus controlling proliferation of malaria parasite. However, the causative gene have not been identified. We generated novel mutant mice strains by the CRISPR/Cas9 system on NC strain. The knock-in strain which has single nucleotide substitution with amino acid substitution (p.89P>R) on Apeh gene showed suppressed parasitemia and prolonged survival. It was revealed that this substitution of Apeh gene is the causative variant which controlling malaria resistance.
Academic Significance and Societal Importance of the Research Achievements	Apeh遺伝子がコードするアシルペプチド加水分解酵素の機能は十分に判明していない。本研究で赤血球内のこの酵素がマラリア原虫の増殖に重要な役割を持っている事が判明すると同時に、未知のマラリア原虫増殖抑制機構が存在することも示した。この新規マラリア抵抗性遺伝子の発見は、マラリアの新規治療薬の開発に繋がる重要な知見であると考えられる。