Nek7-KO Mouse

NEK7, short for NIMA-related kinase 7, is a serine/threonine kinase and the smallest in the mammalian NEK family. It has a physiological role in regulating the cell cycle and promoting mitosis. Notably, it is also involved in the activation of the NLRP3 inflammasome, which is crucial for the innate immune response [1].

Mouse chimaeras reconstituted with Nek7(-/-) haematopoietic cells demonstrated that NEK7 is essential for NLRP3 inflammasome activation in vivo. In the absence of NEK7, caspase-1 activation and IL-1β release in response to NLRP3-activating signals were abrogated, indicating its critical role downstream of potassium efflux in regulating NLRP3 oligomerization and activation [3]. In IBD, NEK7 knockdown abolished ATP + LPS-induced pyroptosis in vitro and improved DSS-induced chronic colitis in vivo, suggesting its role in modulating pyroptosis through interaction with NLRP3 [2].

In conclusion, NEK7 is a multifunctional kinase involved in cell cycle regulation and NLRP3 inflammasome activation. Studies using NEK7 knockout mouse models have revealed its significance in inflammatory diseases like IBD and in the activation mechanism of the NLRP3 inflammasome, providing potential therapeutic targets for NLRP3-related diseases [1,2,3].

References:

1. Wang, Jin, Chen, Simeng, Liu, Min, Zhang, Min, Jia, Xiaoyi. 2022. NEK7: a new target for the treatment of multiple tumors and chronic inflammatory diseases. In Inflammopharmacology, 30, 1179-1187. doi:10.1007/s10787-022-01026-7. https://pubmed.ncbi.nlm.nih.gov/35829941/

2. Chen, Xueliang, Liu, Ganglei, Yuan, Yuanyuan, Wang, Shalong, Yuan, Lianwen. 2019. NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling. In Cell death & disease, 10, 906. doi:10.1038/s41419-019-2157-1. https://pubmed.ncbi.nlm.nih.gov/31787755/

3. He, Yuan, Zeng, Melody Y, Yang, Dahai, Motro, Benny, Núñez, Gabriel. 2016. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. In Nature, 530, 354-7. doi:10.1038/nature16959. https://pubmed.ncbi.nlm.nih.gov/26814970/