Senp8-flox Mouse

Senp8, also known as human deneddylase-1, is a SUMO peptidase family member that specifically acts as a deneddylating enzyme. Neddylation is a cellular process where NEDD8 is conjugated to target proteins, and Senp8 counteracts this process. It plays a key role in regulating multiple biological pathways, such as those related to neuronal development, cell cycle progression, and the immune response [1,5,6]. Genetic models, like KO/CKO mouse models, are valuable for studying Senp8's functions.

In neuronal development, Senp8 negatively regulates neurite outgrowth through pathways including actin dynamics, Wnt/β-catenin signaling, and autophagic processes, which in turn impairs excitatory synapse maturation [1]. In acute lymphoblastic leukemia (ALL), etoposide-induced Senp8 confers feedback drug resistance, as overexpressing Senp8 reduces ALL cells' chemosensitivity to etoposide, while knockdown can sensitize them [4]. In colon cancer, Senp8-mediated SHP2 deneddylation via the CD47/SIRPα axis mediates tumor immunosuppression [2]. In hepatitis B virus (HBV) propagation, overexpression of Senp8, which cleaves conjugated NEDD8, suppresses HBV propagation [3].

In conclusion, Senp8 is essential in regulating neddylation-related biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in neurodevelopmental disorders, ALL, colon cancer, and HBV-related diseases. Understanding Senp8's functions provides potential therapeutic targets for these diseases.