Oit3-KO Mouse

Oit3, also known as liver-specific zona pellucida domain-containing protein (LZP), is involved in multiple biological functions and disease-related processes. In the body, it may be associated with maintaining urate homeostasis in the renal tubule and has been linked to macrophage polarization and immune-related pathways. Genetic models, such as the Oit3-CreERT2 transgenic mice, can be valuable for studying its functions in specific cell types [1,5].

In research, Oit3-null mice showed lower serum uric acid levels and increased urinary uric acid excretion, suggesting that Oit3 maintains urate homeostasis by regulating uric acid excretion and reabsorption in the renal tubule in cooperation with THP [5]. In hepatocellular carcinoma (HCC), overexpression of Oit3 in macrophages promoted PD-L1 expression via NF-κB signaling, inhibited T-cell infiltration in the tumor microenvironment, and facilitated HCC progression [3]. Also, low expression of Oit3 in HCC was associated with poor clinical outcomes, and ectopic expression of Oit3 inhibited HCC cell proliferation, migration, and invasion by inducing ferroptosis through regulating arachidonic acid metabolism [4]. In addition, Oit3-overexpressing macrophages enhanced the migration and invasion of co-cultured cancer cells and promoted tumorigenesis in vivo [2]. Moreover, in the context of acute lung injury after cardiac surgery, Oit3-enriched extracellular vesicles alleviated the injury by promoting NLRP3 ubiquitination [6].

In conclusion, Oit3 plays essential roles in maintaining urate homeostasis in the kidney and has significant impacts on the development and progression of diseases like hepatocellular carcinoma and acute lung injury after cardiac surgery. Studies using gene-knockout or transgenic mouse models have been crucial in revealing these functions, providing insights into potential therapeutic targets for related diseases.