Animal Models for the Investigation of P2X7 Receptors
Ronald Sluyter1,2, Sahil Adriouch3, Stephen J Fuller4
1Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.
Abstract:
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.
Insights
Animal models are crucial for understanding the P2X7 receptor
Area of Science:
- Pharmacology
- Immunology
- Neuroscience
Background:
- The P2X7 receptor (P2X7R) is a key ion channel involved in numerous physiological and pathophysiological processes.
- Understanding P2X7R function is vital for developing treatments for various diseases.
Purpose of the Study:
- To review the significant contributions of animal models to P2X7R research.
- To highlight the development of P2X7R-targeted tools and therapeutics.
Main Methods:
- Overview of P2X7R distribution, roles, and properties.
- Analysis of animal model applications in P2X7R research.
- Review of P2X7R knockout and humanized models.
Main Results:
- Animal studies have facilitated the creation of P2X7R-specific antibodies, nanobodies, recombinant receptors, and radioligands.
- Various animal models, including mice, rats, and other species, have been instrumental in preclinical P2X7R research.
- Pharmacokinetic testing of P2X7R antagonists has been advanced through animal studies.
Conclusions:
- Animal models are indispensable for advancing P2X7R research and therapeutic development.
- The use of diverse animal models provides comprehensive insights into P2X7R function in health and disease.
