Functional investigation of Cables2, a novel transcription cofactor regulating Nanog expression through Smad2 activation, during germ cell development

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16020
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: University of Tsukuba
• Principal Investigator: DINH T.H.TRA 筑波大学, 医学医療系, 助教 (30816476)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Cables2 / embryogenesis

Outline of Final Research Achievements

CDK5 and Abl enzyme substrate 2 (Cables2), a member of the Cables family, is ubiquitously expressed in mouse embryonic and reproductive organs at the RNA level, suggesting the existence and contribution of Cables2 in embryonic and germ cell development. However, in vivo function of Cables2 remains unclear. Therefore, in this study, we aimed to explore the role of Cables2 using mouse models.
Using genetically modified mouse models, we found that the entire Cables2 locus is essential for early mouse embryogenesis. Transcriptome profiling comparison revealed that Cables2 indeed involved in male gonad development and fundamental signaling pathways such as Wnt and P53. In addition, we successfully generated a Cables2 knock-in reporter model in which Cables2 is demonstrated to be expressed in mouse testis and ovary, the main reproductive organs. Generally, this study highlights the sophisticated role of Cables2 in mouse development.

Free Research Field

42040

Academic Significance and Societal Importance of the Research Achievements

This study firstly report about the essential of Cables2 locus in mouse development. Cables2 is clarified to be expressed in various mouse tissues including testis, ovary, brain, etc. In addition, this study focus attention on the need to validate target knock-out genes in lethal phenotypes.