Ing3-flox Mouse

ING3, a member of the Inhibitor of Growth (ING) family, is a histone-modifying protein involved in regulating cell proliferation, senescence, apoptosis, chromatin remodeling, and DNA repair [3,7]. It is a stoichiometric component of the NuA4-Tip60 MYST histone acetyl-transferase complex, which is responsible for histone H2A and H4 acetylation [3]. ING3 also plays a role in the DNA damage response pathway by being required for ATM activation and subsequent DNA repair [5].

In various cancers, ING3 shows different roles. In lung adenocarcinoma, down-regulated ING3 expression is observed, and up-regulation of ING3 inhibits cell proliferation, migration, invasion, and induces cell cycle arrest by negatively regulating ITGB4 expression to inactivate Src/FAK signaling [2]. In breast cancer, nuclear ING3 expression is reduced, and its down-regulation is correlated with poor prognosis, and overexpression of ING3 inhibits cell migration and invasion [1,4]. However, in prostate cancer, ING3 promotes cancer growth by activating the androgen receptor, and high levels of ING3 predict shorter patient survival in a low AR subgroup [6]. In a transgenic mouse model with insertional mutation of Ing3, homozygous mutants are embryonically lethal, showing growth retardation and severe developmental disorders, especially in neural tube closure and primary brain vesicle formation, indicating ING3 is essential for normal embryonic development [7].

In conclusion, ING3 has diverse functions in different biological processes and disease conditions. It plays crucial roles in embryonic development, and its dysregulation is associated with cancer progression. The use of mouse models, such as the Ing3-disrupted transgenic mouse, has been instrumental in understanding its role in embryonic development and in revealing its dual nature as a potential tumor suppressor or oncogene in different cancers.