G2e3-flox Mouse

G2E3, a G2/M-phase-specific E3 ubiquitin protein ligase, contains a conserved HECT domain and is likely to function as a ubiquitin ligase. It is a nucleo-cytoplasmic shuttling protein with a novel nuclear export domain and a nucleolar localization signal, suggesting its role in cell cycle regulation and the cellular response to DNA damage [1]. It also has been implicated in early embryonic development, preventing apoptotic death [2].

G2E3 knockout (KO) mouse models have provided valuable insights. G2E3 null embryos die prior to implantation due to massive apoptosis in blastocysts [2]. G2e3 KO mice also exhibit increased body fat, obesity, and glucose intolerance, suggesting that obesity-associated variants near human G2E3 may decrease G2E3 activity [4]. In breast cancer, high G2E3 expression is associated with worse survival outcomes, and genes co-expressed with G2E3 may be enriched in cancer-related signaling pathways like E2F, PI3K/AKT/mTOR, and DNA repair pathways [3]. Loss of G2E3 sensitizes tumor cells to chemotherapy, as it leads to decreased DNA damage response markers and increased apoptosis and decreased proliferation of cancer cells [5].

In summary, G2E3 is essential for early embryonic development by preventing apoptosis. Its dysregulation is associated with obesity and poor prognosis in breast cancer. The G2E3 KO mouse models have been crucial in uncovering these roles, highlighting its potential as a therapeutic target in cancer and a gene of interest in obesity-related research.