Establishment of research platform in mouse models linking the causative genes of fetal edema to prognosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20615
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Niigata University
• Principal Investigator: Sugiyama Akira 新潟大学, 医歯学総合研究科, 助教 (10908437)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 浮腫 / 胎児 / リンパ管 / 遺伝子改変マウス

Outline of Final Research Achievements

Fetal edema is detected by ultrasonography in the first trimester of pregnancy. However, the causes and prognosis have been elucidated in many clinical cases. In this study, we identified candidate causative genes of fetal edema by using mutagenized mice, and generated knockout mice for some of the candidate causative genes. As a result, three genes were found as possible causative genes of fetal edema. Anomalies in dermal lymphatic vascular morphology were observed in the knockout fetuses for each gene. In addition, for one of these genes, suppression of gene expression in cultured lymphatic endothelial cells resulted in decreased gene expression of VEGFR3 (vascular endothelial growth factor receptor 3) and decreased the number of viable cells.

Free Research Field

脈管発生学

Academic Significance and Societal Importance of the Research Achievements

本研究により3遺伝子について胎児浮腫の新たな原因遺伝子である可能性が見出された。また、3遺伝子のうち1遺伝子についてはリンパ管内皮細胞の機能調節を介してリンパ管形成を制御することを明らかにした。本研究で樹立したノックアウトマウス系統について更に解析を進めることにより、リンパ管形成の制御機構や胎児浮腫の病態・予後の解明に繋がる。ノックアウトマウス解析により得られた知見は、胎児浮腫の正確な診断法を開発する上での基盤となることが期待される。