Generation of animal model and functional analysis of EYS, a retinitis pigmentosa-causing gene, in zebrafish

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16995
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: National Rehabilitation Center for Persons with Disabilities
• Principal Investigator: Takita Shimpei 国立障害者リハビリテーションセンター(研究所), 研究所 感覚機能系障害研究部, 流動研究員 (90781261)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Zebrafish eys / lrp5 / rbp1 / eys-related genes / Functional analysis

Outline of Final Research Achievements

The human eyes shut homolog (EYS) gene is a major cause of retinitis pigmentosa, accounting for about 30% of all cases, in the Japanese population, however, there is currently no treatment. In this study, the grant recipient used zebrafish as an animal model by generating eys knockout (eys-/-) and analyzing function of EYS protein. Photoreceptor degeneration was observed in the mutant and expression levels of several genes were remarkably reduced.
In addition, in the digenic eys+/-; low-density lipoprotein (LDL)-related receptor-5 (lrp5)+/- eye, expression level of retinol binding protein 1 (rbp1), the protein important for the retinoid cycle, was remarkably reduced.

Free Research Field

眼科学関連

Academic Significance and Societal Importance of the Research Achievements

ヒトeyes shut homolog (EYS)遺伝子は、日本人常染色体潜性網膜色素変性の約3割を占める主要原因である。本研究によりゼブラフィッシュeys-/-眼球で確かに視細胞変性が観察されたことから、ヒトでの遺伝子解析結果が裏付けられた。
そして、ヒトとゼブラフィッシュとでEYSの転写産物を詳細に解析し主要な発現転写産物を明らかにすることで、遺伝子解析・治療、機能解析の基盤を整えた。
また、これまで網膜色素上皮におけるall-trans retinolの取り込みは良く分かっていなかったが、2遺伝子性eys+/-; lrp5+/-を解析することで、LRP5が関与する可能性が強く示唆された。