Ripk4-KO Mouse

Ripk4, short for receptor-interacting protein kinase 4, is a member of the RIPK family. It was originally described as an interaction partner of protein kinase C (PKC) β and PKCδ. Ripk4 is a key regulator in multiple biological processes, including keratinocyte differentiation, cutaneous inflammation, and cutaneous wound repair. It is involved in several signaling pathways such as NF-κB, Wnt/β-catenin, and RAF/MEK/ERK pathways, which interact to form a complex network [2].

Specific ablation of Ripk4 in kidney proximal tubules protects mice from acute kidney injury induced by cisplatin and renal ischemia/reperfusion, suggesting its role in oxidative stress and ferroptotic death [1]. In ovarian cancer, Ripk4 silencing significantly inhibits intraperitoneal tumor growth, invasion, and vascular mimicry, and down-regulation of Ripk4 inhibits the epithelial-mesenchymal transition of ovarian cancer cells both in vitro and in vivo [3]. In cutaneous squamous cell carcinoma, depletion of Ripk4 parallels higher malignancy potential, although it cannot reverse the radiation resistance of A431 cells in vitro [4].

In conclusion, Ripk4 is a crucial regulator in various biological processes and diseases. The use of gene knockout (KO) or conditional knockout (CKO) mouse models has been instrumental in revealing its functions in oxidative stress, ferroptotic death, tumorigenesis, and cell-cell adhesion. These findings contribute to our understanding of the underlying mechanisms of related diseases and may provide potential therapeutic targets.