Ing3-KO Mouse

ING3, a member of the ING family, is involved in regulating the transcriptional state of chromatin. It recruits remodeling complexes to sites with histone H3 trimethylated at Lysine 4 (H3K4me3) through its C-terminal Plant HomeoDomain (PHD), and facilitates histone acetylation by the NuA4-Tip60 MYST histone acetyl transferase complex. It plays crucial roles in cell cycle control, senescence, DNA repair, cell proliferation, and apoptosis, and is important for normal embryonic development [1,4,6,8].

A transgenic mouse strain with insertional mutation of an UbC-mCherry expression cassette into the endogenous Ing3 locus led to disruption of ING3 protein expression. Homozygous mutants were embryonically lethal, showing growth retardation and severe developmental disorders, especially in neural tube closure and primary brain vesicle formation, indicating ING3 is essential for prenatal brain formation [8]. In human cells, ING3-depleted cells are sensitive to DNA damage, as ING3 is recruited to DNA double-strand breaks and required for ATM activation, which is crucial for DNA repair by non-homologous end joining (NHEJ) or homologous recombination (HR), and for immunoglobulin class switch recombination (CSR) [6]. In prostate cancer, ING3 promotes cancer growth by activating the androgen receptor, while in other cancers like breast and lung adenocarcinoma, it acts as a tumor suppressor, inhibiting cell migration, invasion, and proliferation [2,3,5,7].

In conclusion, ING3 has diverse functions. Its role in DNA repair and embryonic development is revealed through gene-knockout mouse models. In disease, it can act as either a tumor suppressor or an oncogene depending on the cancer type. Studies on ING3 contribute to understanding cancer progression and potentially developing new cancer treatment strategies.