Gpx2-KO Mouse

GPX2, also known as GSHPx-GI, is a selenoenzyme with glutathione peroxidase activity. Among the four Se-GPX isozymes (GPX1-4), it is closely related to GPX1 in terms of structure, substrate specificities, and subcellular localization. GPX2 expression is regulated by multiple pathways such as NRF2, WNT, p53, RARE, and is mainly found in epithelial tissues, especially in stem cell and proliferative compartments [1]. It plays a role in maintaining hydroperoxidase activity balance along with GPX1, peroxiredoxins, and catalase, and is involved in important biological processes like mucosal homeostasis and carcinogenesis [1,3]. Gene knockout mouse models can be valuable for studying its functions.

In gene function studies, knocking out both Gpx1 and Gpx2 in mice led to ileocolitis, indicating their combined importance in maintaining normal intestinal function [1]. In an inflammation-associated colon carcinogenesis mouse model (AOM/DSS), GPX2 deletion increased inflammation and tumor development but decreased tumor size, showing its Janus-faced role in carcinogenesis [3]. In hepatocellular carcinoma, regulating GPX2 levels affected lenvatinib-induced ROS levels and apoptosis, and low GPX2-expressing patients had a higher objective response rate to lenvatinib therapy [2].

In conclusion, GPX2 is a key selenoenzyme involved in maintaining hydroperoxidase balance, mucosal homeostasis, and playing a complex role in carcinogenesis. Studies using gene knockout mouse models have revealed its significance in intestinal function and cancer-related processes, providing insights into its biological functions and potential as a therapeutic target in diseases like hepatocellular carcinoma.