C57BL/6JCya-Usp24^em1flox/Cya

Usp24, a deubiquitinase, plays diverse roles in various biological processes and diseases. It is involved in pathways such as NF-κB, autophagy, and regulation of protein stability, which are crucial for maintaining cell homeostasis and influencing disease progression [1-7, 9, 10]. Genetic models, like gene knockout in mice, are valuable for studying its functions.

In a high-fat diet and streptozotocin-induced mouse model of diabetic cardiomyopathy (DCM), knockdown of Usp24 reduced NF-κB levels, alleviating ferroptosis, as indicated by decreased fatty acid-CoA ligase 4 (FACL4), increased ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 (SLC7A11), improved antioxidant capacity, and enhanced cell viability [1]. In a gefitinib-induced drug-resistant mouse model with doxycycline-induced EGFRL858R lung cancer, targeting Usp24 by USP24-i-101 inhibited drug resistance and activated autophagy, but this effect was abolished after autophagy inhibition [2]. In hepatocellular carcinoma, knockdown and overexpression studies showed that Usp24 regulates autophagy-dependent ferroptosis by reducing the K48-linked ubiquitination of Beclin1 [3]. In another study on hepatocellular carcinoma, Usp24 promoted tumorigenesis by deubiquitinating and stabilizing TRAF2, activating the AKT/NF-κB signaling pathway [4].

In conclusion, Usp24 is involved in multiple biological processes, with its dysregulation contributing to diseases like DCM, cancer drug resistance, and hepatocellular carcinoma. Gene knockout and other functional studies in mouse models have been instrumental in uncovering its role in these disease conditions, providing potential therapeutic targets for treatment.