Ezh2-flox Mouse

Ezh2, short for Enhancer of zeste homolog 2, is the catalytic subunit of the polycomb repressive complex 2 (PRC2) [2,5,6]. Its main function is to catalyze the methylation of H3 histone at lysine 27 (H3K27me3), which usually leads to the repression of target genes, such as tumor suppressor genes [2]. Ezh2 is involved in multiple cellular processes including the cell cycle, DNA damage repair, cell differentiation, autophagy, apoptosis, and immunological modulation [2].

In the context of diseases, Ezh2 has been widely studied. In triple-negative breast cancer (TNBC), functional EZH2 (H3K27me3) promotes peritoneal metastasis by upregulating KRT14, and EZH2 knockdown or H3K27me3 inhibition reduces metastasis [1]. In sepsis-induced acute kidney injury, Ezh2 knockout mice showed reduced renal inflammation and macrophage infiltration. Silencing Ezh2 protected renal function by relieving transcriptional inhibition of Sox9, activating the Wnt/β-catenin pathway [3]. In myeloid malignancies, Ezh2 dysregulation is highly tumorigenic, with loss-of-function mutations affecting certain patients, and in chronic myeloid leukemia, EZH2 overexpression is often observed [4].

In conclusion, Ezh2 is a crucial regulator in multiple biological processes and disease conditions. Gene knockout models, like Ezh2 knockout mice, have significantly contributed to understanding its role in diseases such as TNBC, sepsis-induced AKI, and myeloid malignancies, providing potential therapeutic targets for these diseases.