https://scholars.lib.ntu.edu.tw/handle/123456789/569620
標題: | Wdhd1 is essential for early mouse embryogenesis | 作者: | Fan, Hsiang-Hsuan Lee, Kuo-Hong YOU-TZUNG CHEN Lin, Li-Jyuan TSUNG-LIN YANG SHU-WHA LIN Yu, I-Shing |
關鍵字: | CRISPR/Cas9; DNA replication; Embryogenesis; Mouse; Proliferation; Wdhd1 | 公開日期: | 五月-2021 | 卷: | 1868 | 期: | 6 | 來源出版物: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 摘要: | WD repeat and HMG-box DNA binding protein 1 (Wdhd1) is the mouse ortholog of budding yeast Chromosome Transmission Fidelity 4 (CTF4), the protein product of which integrates the MCM2-7 helicase and DNA polymerase α/primase complex to initiate DNA replication. Previous work in fruit flies, Xenopus egg extracts, and human cell lines suggest that Wdhd1 is required for efficient DNA synthesis. However, rigorous in vivo functional studies on Wdhd1 in mammals are unavailable. In the present study, we have successfully generated a Wdhd1 null allele in mice through CRISPR/Cas9-mediated genome editing to investigate the role of Wdhd1 in embryogenesis in vivo. We characterized Wdhd1 expression using quantitative reverse-transcription polymerase chain reaction, and assessed embryonic cell proliferation by histology in both pre- and peri-implantation embryos. While Wdhd1 heterozygous mutant mice were grossly normal and fertile, we observed a reduction in cell proliferation by the gastrulation stage in Wdhd1 homozygous null mutant embryos which severely hampered their growth and viability. These results indicate that Wdhd1 plays a major role in cell proliferation during embryogenesis in mice. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/569620 | ISSN: | 01674889 | DOI: | 10.1016/j.bbamcr.2021.119011 |
顯示於: | 基因體暨蛋白體醫學研究所 |
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