P2rx7, also known as the purinergic receptor P2X 7, is a nonselective ligand-gated homotrimeric cation channel. It functions as a danger sensor, detecting extracellular nucleotides from injured cells and triggering an inflammatory cascade. It is expressed in immune cells and is involved in pathogen surveillance, cell-mediated responses to infectious organisms, and also participates in various physiological and pathological processes such as pain, CNS and psychiatric disorders, and cancer [2,3]. Gene knockout (KO) and conditional knockout (CKO) mouse models have been valuable in studying its functions.

In epilepsy, upregulation of P2rx7 due to downregulation of microRNA-211-5p increases neuronal activity during epileptic seizures. Genetic-silencing of P2rx7 significantly reduced the seizure score and duration in murine models, suggesting that the miR-211-5p/P2rx7 axis is a novel target for suppressing epilepsy [1]. In osteosarcoma, knockout of P2rx7 using Nuclease technology technology showed that P2rx7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization, indicating it could be a potential diagnostic and/or therapeutic target [5]. In chronic nonbacterial osteomyelitis (CNO), rare presumably damaging P2rx7 variants identified in patients were associated with altered inflammasome assembly and reduced pyroptosis in patient-derived monocytes and genetically modified THP-1 cells, suggesting P2rx7 variants may be a CNO risk factor [4].

In conclusion, P2rx7 plays crucial roles in multiple biological processes and diseases. Studies using KO and CKO mouse models have revealed its functions in epilepsy, osteosarcoma, and CNO, among others. These models have been instrumental in understanding how P2rx7 contributes to disease pathogenesis, providing potential targets for therapeutic intervention in these disease areas.

References:

1. Li, Xueying, Quan, Pusheng, Si, Yao, Yang, Fan, Yao, Lifen. 2024. The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress. In Journal of neuroinflammation, 21, 13. doi:10.1186/s12974-023-03009-z. https://pubmed.ncbi.nlm.nih.gov/38191407/

2. Soare, Alexandra Y, Freeman, Tracey L, Min, Alice K, Osota, Elizabeth O, Swartz, Talia H. 2021. P2RX7 at the Host-Pathogen Interface of Infectious Diseases. In Microbiology and molecular biology reviews : MMBR, 85, . doi:10.1128/MMBR.00055-20. https://pubmed.ncbi.nlm.nih.gov/33441488/

3. Young, Chris N J, Górecki, Dariusz C. 2018. P2RX7 Purinoceptor as a Therapeutic Target-The Second Coming? In Frontiers in chemistry, 6, 248. doi:10.3389/fchem.2018.00248. https://pubmed.ncbi.nlm.nih.gov/30003075/

4. Charras, Amandine, Hofmann, Sigrun R, Cox, Allison, Ferguson, Polly J, Hedrich, Christian M. 2024. P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO). In Journal of autoimmunity, 144, 103183. doi:10.1016/j.jaut.2024.103183. https://pubmed.ncbi.nlm.nih.gov/38401466/

5. Sheng, Gaohong, Gao, Yuan, Ding, Qing, Wu, Hua, Yang, Yong. 2023. P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization. In Journal of translational medicine, 21, 132. doi:10.1186/s12967-023-03985-z. https://pubmed.ncbi.nlm.nih.gov/36803784/