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Knockout and Knock-in Mouse Models to Study Purinergic Signaling

  • Robin M. H. Rumney
  • Dariusz C. GóreckiEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2041)

Abstract

Purinergic signaling involves extracellular purines and pyrimidines acting upon specific cell surface purinoceptors classified into the P1, P2X, and P2Y families for nucleosides and nucleotides. This widespread signaling mechanism is active in all major tissues and influences a range of functions in health and disease. Orthologs to all but one of the human purinoceptors have been found in mouse, making this laboratory animal a useful model to study their function. Indeed, analyses of purinoceptors via knock-in or knockout approaches to produce gain or loss of function phenotypes have revealed several important therapeutic targets. None of the homozygous purinoceptor knockouts proved to be developmentally lethal, which suggest that either these receptors are not involved in key developmental processes or that the large number of receptors in each family allowed for functional compensation. Different models for the same purinoceptor often show compatible phenotypes but there have been examples of significant discrepancies. These revealed unexpected differences in the structure of human and mouse genes and emphasized the importance of the genetic background of different mouse strains. In this chapter, we provide an overview of the current knowledge and new trends in the modifications of purinoceptor genes in vivo. We discuss the resulting phenotypes, their applications and relative merits and limitations of mouse models available to study purinoceptor subtypes.

Key words

Knock-in Knockout Genetically modified animals Purinergic signaling Purinoceptor 

Notes

Acknowledgments

The authors would like to acknowledge the Polish Ministry of National Defence project “Kościuszko” no: 523/2017/DA and the EU COST Program (BM1406).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.School of Pharmacy and Biomedical SciencesUniversity of PortsmouthPortsmouthUK
  2. 2.Military Institute of Hygiene and EpidemiologyWarsawPoland

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