C57BL/6JCya-Usf2^em1flox/Cya

Usf2, also known as upstream stimulatory factor 2, is a basic helix-loop-helix-leucine-zip transcription factor. It is involved in various biological processes by regulating gene transcription. It participates in pathways such as TGF-β signaling, autophagy, and pyroptosis, and is of great biological importance in diseases like sepsis-induced acute kidney injury, colorectal cancer, and chronic lymphocytic leukemia [1-4]. Genetic models, especially gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable in studying its functions.

In sepsis-induced acute kidney injury, knockdown of Usf2 downregulates THBS1, inhibits the TGF-β/Smad3 signaling pathway, and reduces pyroptosis, thus ameliorating the injury [1]. In colorectal cancer, TGF-β promotes EMT and metastasis through the Usf2/S100A8 axis, while extracellular S100A8 suppresses this axis, with Usf2 being an important switch in the feedback loop [2]. In chronic lymphocytic leukemia, Usf2 promotes autophagy and proliferation by inhibiting STUB1-induced NFAT5 ubiquitination, and its knockdown weakens the disease progression in xenotransplantation model of nude mice [3]. In lupus nephritis, knockdown of Usf2 inhibits podocyte pyroptosis and attenuates kidney injury [4]. In cerebral ischemia-reperfusion injury, Usf2 deficiency promotes autophagy to alleviate the injury through suppressing YTHDF1-m6A-mediated Cdc25A translation [5].

In conclusion, Usf2 plays diverse and crucial roles in multiple biological processes and disease conditions. The KO/CKO mouse models and other loss-of-function experiments have revealed its functions in inflammation-related kidney injuries, cancer metastasis, autophagy regulation in leukemia and cerebral ischemia-reperfusion injury, and podocyte pyroptosis in lupus nephritis. These findings help in understanding the molecular mechanisms underlying these diseases and may provide potential therapeutic targets.