Ets2-KO Mouse

Ets2, short for V-ets erythroblastosis virus E26 oncogene homolog 2, is a transcription factor belonging to the E26 transformation-specific sequence (ETS) domain family. It plays a crucial role in regulating various cellular processes such as cell proliferation, differentiation, apoptosis, and is associated with multiple signaling pathways. Its dysregulation is linked to numerous diseases, highlighting its biological importance [1,3,4]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying Ets2's function.

In cardiac hypertrophy, conditional deletion of Ets2 in mouse cardiomyocytes protects against pressure-overload-induced cardiac hypertrophy, and silencing of Ets2 in the hearts of calcineurin transgenic mice attenuates hypertrophic growth and contractile dysfunction. Ets2 forms a complex with NFAT to stimulate transcriptional activity of hypertrophy-related genes, revealing its role in the calcineurin/NFAT pathway-driven cardiac hypertrophy [1]. In liver failure, myeloid-specific Ets2 deficiency in liver failure mice leads to deterioration of biofunctions and increased expression of pro-inflammatory cytokines, indicating that Ets2 alleviates liver failure by down-regulating the inflammatory response [2]. In renal fibrosis, knockdown of Ets2 in human proximal tubular epithelial cells abrogates TGF-β1-mediated expression of profibrogenic factors, suggesting Ets2 promotes epithelial-to-mesenchymal transition in renal fibrosis [5].

In conclusion, Ets2 is a key transcription factor involved in diverse biological processes. Studies using KO/CKO mouse models have demonstrated its significance in cardiac hypertrophy, liver failure, and renal fibrosis. These findings enhance our understanding of disease mechanisms and may provide potential therapeutic targets for these diseases.

References:

1. Luo, Yuxuan, Jiang, Nan, May, Herman I, Gillette, Thomas G, Hill, Joseph A. 2021. Cooperative Binding of ETS2 and NFAT Links Erk1/2 and Calcineurin Signaling in the Pathogenesis of Cardiac Hypertrophy. In Circulation, 144, 34-51. doi:10.1161/CIRCULATIONAHA.120.052384. https://pubmed.ncbi.nlm.nih.gov/33821668/

2. He, Lulu, Cai, Qun, Liang, Xi, Jiang, Jing, Li, Jun. . ETS2 alleviates acute-on-chronic liver failure by suppressing excessive inflammation. In Journal of medical virology, 95, e28710. doi:10.1002/jmv.28710. https://pubmed.ncbi.nlm.nih.gov/36975761/

3. Martinez, Luis Alfonso. 2016. Mutant p53 and ETS2, a Tale of Reciprocity. In Frontiers in oncology, 6, 35. doi:10.3389/fonc.2016.00035. https://pubmed.ncbi.nlm.nih.gov/26925389/

4. Choi, Yunsik, Lee, Yuri, Kim, Jin Seo, Zhang, Peijing, Kim, Jongchan. 2023. USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity. In Biomolecules, 13, . doi:10.3390/biom13101475. https://pubmed.ncbi.nlm.nih.gov/37892157/

5. Yao, Fang, Wang, Xiaojing, Cui, Zhong-Kai, Wu, Bingyi, Bai, Xiaochun. 2019. ETS2 promotes epithelial-to-mesenchymal transition in renal fibrosis by targeting JUNB transcription. In Laboratory investigation; a journal of technical methods and pathology, 100, 438-453. doi:10.1038/s41374-019-0331-9. https://pubmed.ncbi.nlm.nih.gov/31641227/