Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.
Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
Int J Mol Sci. 2023 May 4;24(9):8225. doi: 10.3390/ijms24098225.
The P2X7 receptor is a trimeric ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate. The study of animals has greatly advanced the investigation of P2X7 and helped to establish the numerous physiological and pathophysiological roles of this receptor in human health and disease. Following a short overview of the P2X7 distribution, roles and functional properties, this article discusses how animal models have contributed to the generation of P2X7-specific antibodies and nanobodies (including biologics), recombinant receptors and radioligands to study P2X7 as well as to the pharmacokinetic testing of P2X7 antagonists. This article then outlines how mouse and rat models have been used to study P2X7. These sections include discussions on preclinical disease models, polymorphic P2X7 variants, P2X7 knockout mice (including bone marrow chimeras and conditional knockouts), P2X7 reporter mice, humanized P2X7 mice and P2X7 knockout rats. Finally, this article reviews the limited number of studies involving guinea pigs, rabbits, monkeys (rhesus macaques), dogs, cats, zebrafish, and other fish species (seabream, ayu sweetfish, rainbow trout and Japanese flounder) to study P2X7.
P2X7 受体是一种三聚体配体门控阳离子通道，由细胞外三磷酸腺苷激活。对动物的研究极大地推动了 P2X7 的研究，并有助于确定该受体在人类健康和疾病中的许多生理和病理生理作用。本文简要概述了 P2X7 的分布、作用和功能特性，讨论了动物模型如何有助于生成 P2X7 特异性抗体和纳米抗体（包括生物制剂）、重组受体和放射性配体，以研究 P2X7 以及对 P2X7 拮抗剂的药代动力学测试。然后，本文概述了如何使用小鼠和大鼠模型来研究 P2X7。这些部分包括对临床前疾病模型、多态性 P2X7 变体、P2X7 敲除小鼠（包括骨髓嵌合体和条件性敲除）、P2X7 报告小鼠、人源化 P2X7 小鼠和 P2X7 敲除大鼠的讨论。最后，本文回顾了涉及豚鼠、兔、猴（恒河猴）、狗、猫、斑马鱼以及其他鱼类（真鲷、牙鲆、虹鳟和日本比目鱼）研究 P2X7 的少数研究。
