Kat6a-flox Mouse

KAT6A, also known as MOZ (monocytic leukemia zinc finger protein) and MYST3, is a histone lysine acetyltransferase belonging to the MYST family. It acetylates histone H3K23 and plays crucial roles in multiple biological processes, including embryonic development, hematopoiesis, and neural stem cell maintenance. It is involved in pathways such as estrogen signaling, cell cycle, Myc, and stem cell pathways [1,2,6]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In cancer research, loss-of-function studies have shown potential therapeutic implications. In acute myeloid leukemia (AML), inhibition of KAT6A in vitro and in vivo led to strong anti-AML phenotypes, suggesting it could be a therapeutic target for AML treatment [3]. In triple-negative breast cancer (TNBC), inhibiting KAT6A in combination with anti-PD-L1 therapy attenuated metastasis in TNBC xenograft-bearing animals [4]. Inhibitors of KAT6A/B, such as WM-8014 and WM-1119, induced cell cycle exit and cellular senescence without DNA damage, and WM-1119 arrested lymphoma progression in mice [5]. High levels of KAT6A promote PARPi resistance in ovarian cancer, and inhibiting its liquid-liquid phase separation restores PARPi sensitivity in vivo and in vitro [7].

In conclusion, KAT6A is essential for various biological processes and is implicated in multiple disease conditions, especially cancer. Studies using KO/CKO mouse models have significantly contributed to understanding its role in cancer, highlighting its potential as a therapeutic target for cancer treatment.