Cnot8-flox Mouse

Cnot8, also known as hPop2/Caf1b/Calif, is a subunit of the Ccr4-Not complex with deadenylase activity. This complex is a key regulator of gene expression in eukaryotic cells, and Cnot8's deadenylase function is involved in mRNA turnover, which impacts various biological processes such as cell proliferation, pluripotency transition, and DNA damage response [2,4,5,6,7].

Knockout (KO) of Cnot8 in mice leads to early embryonic lethality, but Cnot8 KO embryonic stem cells (ESCs) can be established. These KO ESCs highly express many genes during differentiation into the formative state, including naïve-like genes, indicating that Cnot8 is essential for eliminating naïve regulation networks and for the naïve-to-formative pluripotency transition [1]. In zebrafish, a mutation in cnot8 increases mRNA levels of a subset of developmental control genes, suggesting its role in vertebrate development [3]. In human cells, depletion of CNOT8 reduces cell viability after ionizing radiation treatment, showing its involvement in the DNA damage response [2].

In summary, Cnot8 is crucial for mRNA turnover and has significant functions in processes like pluripotency transition, development, and DNA damage response. Studies using KO mouse models and other genetic models have revealed its essential roles, which are relevant to understanding embryonic development and cellular responses to DNA damage [1,2,3].