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Publication : Wdhd1 is essential for early mouse embryogenesis.

First Author  Fan HH Year  2021
Journal  Biochim Biophys Acta Mol Cell Res Volume  1868
Issue  6 Pages  119011
PubMed ID  33716172 Mgi Jnum  J:306382
Mgi Id  MGI:6711882 Doi  10.1016/j.bbamcr.2021.119011
Citation  Fan HH, et al. (2021) Wdhd1 is essential for early mouse embryogenesis. Biochim Biophys Acta Mol Cell Res 1868(6):119011
abstractText  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 alpha/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.
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