Generation of SIN3A mutant knock-in mice using GONAD method and searching of target molecule of breast cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K16255
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Yamaguchi University
• Principal Investigator: Watanabe Kenji 山口大学, 大学研究推進機構, 助教 (50711264)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 乳がん / SIN3A

Outline of Final Research Achievements

The estrogen receptor (ER), which exhibits high expression in over half of breast cancers, has become one of the therapeutic targets due to its involvement in cell proliferation. To detect gene mutations that increase ER expression, we classified samples from breast cancer patients into high-expression and low-expression groups based on ER expression and performed exome analysis using next-generation sequencing. As a result, we found that the detected nonsense mutation in SIN3A promotes cell proliferation through increased ER expression. To extensively investigate the functionality of SIN3A in vivo, we initiated the creation of SIN3A mutant knock-in mice using the GONAD method. Through careful consideration of the conditions, we successfully generated genetically modified mice using the GONAD method.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

私たちは、SIN3A 変異が乳がん細胞の増殖を促進することを明らかにした。乳がんにおける SIN3A の機能をさらに詳細に明らかにするためには、in vivo モデルを確立し、生体に近い系で解析することが一番の近道である。しかしながら現在、SIN3A の機能を解析できるモデル動物は存在しない。本研究は、GONAD法を用いてノックインマウスを作成し、世界初の SIN3A の機能を解析できるモデルマウスを確立するものである。GONAD法を用いて遺伝子改変マウスの作成に成功した。