2021 Fiscal Year Annual Research Report
Functional investigation of Cables2, a novel transcription cofactor regulating Nanog expression through Smad2 activation, during germ cell development
| Project/Area Number |
19K16020
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| Research Institution | University of Tsukuba |
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Principal Investigator |
DINH T.H.TRA 筑波大学, 医学医療系, 助教 (30816476)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Cables2 / mouse / embryogenesis |
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| Outline of Annual Research Achievements |
The conventional Cables2 knock-out (KO) embryos, in which entire Cables2 locus was targeted disruption, showed the lethality at the gastrulation stage of mouse development. Therefore, to analyse the function of Cables2 in primordial germ cell (PGC) and germ cell development, floxed Cables2 mice, which loxP sites flanking exon1 of Cables2, were mated with Nanos3-Cre and Gdf9-Cre mouse lines. Unfortunately, there is no any abnormal phenotype observed in Cables2 conditional KO. To further re-confirm the lethal phenotype, Cables2 exon1 deletion mice were exclusively intercrossed and propagated. Unexpectedly, viable and fertile homozygous Cables2 exon1 deletion mice were obtained, which is contrary to entire locus Cables2 phenotype. This surprising result indicates an inconsistent function of Cables2 in embryogenesis.
On the other hands, we found that targeted disruption of the entire Cables2 locus caused growth retardation and enhanced apoptosis at the gastrulation stage and then induced embryonic lethality in mice. Comparative transcriptome analysis revealed that Cables2 locus deletion affected the gene expression of Rps21, abutting on the Cables2 locus, and p53 signaling pathways in embryogenesis.
This study sheds light on the importance of Cables2 locus in embryonic development and contribute to the comprehensive understanding of Cables2 function in mouse.
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