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Knockout and Knock-in Mouse Models to Study Purinergic Signaling

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Purinergic Signaling

Part of the book series: Methods in Molecular Biology ((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.

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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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Authors and Affiliations

  1. School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK

    Robin M. H. Rumney & Dariusz C. Górecki

  2. Military Institute of Hygiene and Epidemiology, Warsaw, Poland

    Dariusz C. Górecki

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  1. Robin M. H. Rumney
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  2. Dariusz C. Górecki
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Correspondence to Dariusz C. Górecki .

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Editors and Affiliations

  1. BioMedical Research Institute of Murcia (IMIB), Clinical University Hospital Virgen de la Arrixaca, Murcia, Spain

    Pablo Pelegrín

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Rumney, R.M.H., Górecki, D.C. (2020). Knockout and Knock-in Mouse Models to Study Purinergic Signaling. In: Pelegrín, P. (eds) Purinergic Signaling. Methods in Molecular Biology, vol 2041. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9717-6_2

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  • DOI: https://doi.org/10.1007/978-1-4939-9717-6_2

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  • Publisher Name: Humana, New York, NY

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