Wdhd1, or WD repeat and HMG-box DNA binding protein 1, is the mouse ortholog of budding yeast Chromosome Transmission Fidelity 4 (CTF4). It integrates the MCM2-7 helicase and DNA polymerase α/primase complex to initiate DNA replication. It is also involved in the PI3K/AKT pathway as a downstream target, with potential implications in cancer development [1,2].

In mouse models, Wdhd1 null allele generated via Nuclease technology-mediated genome editing showed that while heterozygous mutant mice were normal and fertile, homozygous null mutant embryos had reduced cell proliferation by the gastrulation stage, hampering their growth and viability, indicating its major role in embryogenesis cell proliferation [1].

In esophageal cancer, its abnormal regulation as a downstream target of AKT may contribute to cancer occurrence [2]. In nasopharyngeal carcinoma, WDHD1 is over-expressed and may control the expression of ITGAV, potentially related to the cell cycle [3]. In lung adenocarcinoma, WDHD1 leads to cisplatin resistance by promoting MAPRE2 ubiquitination [4]. In PTEN-inactive triple-negative breast cancer, WDHD1 is essential for cell survival [5].

In conclusion, Wdhd1 is crucial for early mouse embryogenesis, especially in cell proliferation. Its role in multiple cancer types, such as esophageal, nasopharyngeal, lung adenocarcinoma, and triple-negative breast cancer, indicates its potential as a biomarker or therapeutic target. Mouse gene knockout models have been instrumental in uncovering these functions, providing valuable insights into disease mechanisms and potential treatment strategies.