Animal Models for the Investigation of P2X7 Receptors

Int J Mol Sci. 2023 May 4;24(9):8225. doi: 10.3390/ijms24098225.

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.

Keywords: P2RX7 gene; P2X7 receptor; P2rx7 gene; immunity; inflammation; isoform; polymorphism; purinergic receptor; transgenic animal; xenograft.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate
  • Animals
  • Dogs
  • Guinea Pigs
  • Humans
  • Macaca mulatta
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Rabbits
  • Rats
  • Receptors, Purinergic P2X7* / genetics
  • Zebrafish*

Substances

  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate

Grants and funding

This research was funded by a University of Wollongong Near Miss Grant (NHMRC Ideas22–2019790) awarded to R.S. Research by A.N. is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Project-ID: 335447717–SFB 1328, A15). The APC was funded by MDPI.