Ripk2-KO Mouse

Ripk2, also known as receptor-interacting protein 2 (RIP2), belongs to the receptor-interacting protein family and is mainly cytoplasmic. It is a dual-specificity kinase widely expressed in human tissues, with high mRNA levels in the spleen, leukocytes, etc. Ripk2 is a key mediator in innate and adaptive immunity, apoptosis, and inflammation. It participates in the Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD) signaling pathways, interacting with tumor necrosis factor receptor (TNFR) [1]. Activation of NOD1/2 by bacterial peptidoglycans recruits Ripk2, leading to the activation of NF-κB and MAPK pathways, and production of pro-inflammatory cytokines [4].

Global genetic deletion of Ripk2 in mice resulted in decreased infarct sizes, reduced neuroinflammatory markers, and improved behavioral outcomes after stroke, suggesting its role in post-stroke neuroinflammation [2]. Conditional deletion of microglial Ripk2 also showed reductive effects on infarct volume and improved behavior within 48 h of injury, indicating microglia-specific functions of Ripk2 in stroke injury [2]. Additionally, an allele encoding a hyperactive form of Ripk2 was associated with increased susceptibility to post-traumatic osteoarthritis in mice, suggesting the NOD/RIPK2 signalling pathway contributes to osteoarthritis susceptibility [3].

In conclusion, Ripk2 is a vital regulator in immune-related signalling pathways. Model-based research, especially gene knockout mouse models, has revealed its roles in diseases such as post-stroke neuroinflammation and osteoarthritis. These findings provide insights into the biological functions of Ripk2 and potential therapeutic targets for related diseases.

References:

1. Tian, Erkang, Zhou, Changhan, Quan, Shuqi, Li, Juan, Zhang, Jifa. 2023. RIPK2 inhibitors for disease therapy: Current status and perspectives. In European journal of medicinal chemistry, 259, 115683. doi:10.1016/j.ejmech.2023.115683. https://pubmed.ncbi.nlm.nih.gov/37531744/

2. Larochelle, Jonathan, Tishko, Ryland J, Yang, Changjun, Khoshbouei, Habibeh, Candelario-Jalil, Eduardo. 2023. Receptor-interacting protein kinase 2 (RIPK2) profoundly contributes to post-stroke neuroinflammation and behavioral deficits with microglia as unique perpetrators. In Journal of neuroinflammation, 20, 221. doi:10.1186/s12974-023-02907-6. https://pubmed.ncbi.nlm.nih.gov/37777791/

3. Jurynec, Michael J, Gavile, Catherine M, Honeggar, Matthew, Kazmers, Nikolas H, Grunwald, David J. 2022. NOD/RIPK2 signalling pathway contributes to osteoarthritis susceptibility. In Annals of the rheumatic diseases, 81, 1465-1473. doi:10.1136/annrheumdis-2022-222497. https://pubmed.ncbi.nlm.nih.gov/35732460/

4. Steinle, Heidrun, Ellwanger, Kornelia, Kufer, Thomas A. . Assaying RIPK2 Activation by Complex Formation. In Methods in molecular biology (Clifton, N.J.), 2523, 133-150. doi:10.1007/978-1-0716-2449-4_9. https://pubmed.ncbi.nlm.nih.gov/35759195/