Kat7-flox Mouse

Kat7, also known as lysine acetyltransferase 7 or HBO1 (MYST2), is a histone acetyltransferase. It plays a crucial role in various biological processes by regulating histone acetylation, which is essential for gene expression. It is involved in pathways such as the MTORC1 pathway, hematopoietic stem cell regulation, and Wnt/β -catenin signaling [2,3,4]. Genetic models are valuable for studying Kat7's functions in different physiological and pathological conditions.

In progeroid hMPC models, inactivation of Kat7 decreased histone H3 lysine 14 acetylation, repressed p15INK4b transcription, and alleviated cellular senescence. Intravenous delivery of lentiviral vectors encoding Cas9/sg-Kat7 alleviated hepatocyte senescence, liver aging, and extended lifespan in aged and progeroid mice [1]. In hematopoietic stem cells, conditional deletion of Hbo1 (encoding Kat7) in mice led to hematopoietic failure, pancytopenia, and rapid loss of hematopoietic progenitors due to abnormal HSC recruitment into the cell cycle [3]. In B-ALL, knockdown of HBO1 inhibited cell viability, proliferation, and G1-S cycle progression while promoting apoptosis, and its overexpression had the opposite effects. A small molecule inhibitor of HBO1, WM-3835, potently inhibited B-ALL progression [4].

In conclusion, Kat7 is essential for regulating histone acetylation and is involved in multiple biological processes. Studies using gene knockout or conditional knockout mouse models have revealed its significant roles in cellular senescence, hematopoiesis, and cancer development. These findings contribute to understanding the underlying mechanisms of related diseases and suggest Kat7 as a potential therapeutic target.