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Knockout and Knock-in Mouse Models to Study Purinergic Signaling
Robin M H Rumney1, Dariusz C Górecki2,3
1School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Methods in Molecular Biology (Clifton, N.J.)
|October 25, 2019
Summary
Mouse models are crucial for studying purinergic signaling, involving purines and pyrimidines acting on cell surface purinoceptors. Genetic modifications in mice reveal therapeutic targets and highlight the importance of genetic background in research.
Area of Science:
- Molecular Biology
- Pharmacology
- Physiology
Background:
- Purinergic signaling utilizes extracellular nucleosides and nucleotides acting on cell surface purinoceptors (P1, P2X, P2Y families).
- This signaling pathway is vital in all major tissues, impacting numerous physiological functions in both health and disease states.
- Mice serve as a valuable model organism due to the presence of orthologs for most human purinoceptors, facilitating functional studies.
Purpose of the Study:
- To provide an overview of current knowledge and emerging trends in modifying purinoceptor genes in vivo.
- To discuss the phenotypes resulting from these genetic modifications.
- To evaluate the applications, merits, and limitations of available mouse models for studying purinoceptor subtypes.
Main Methods:
- Utilizing knock-in or knockout mouse models to create gain or loss of function phenotypes for purinoceptors.
- Analyzing phenotypes resulting from genetic modifications of purinoceptor genes.
- Comparing results across different mouse strains to assess the impact of genetic background.
Main Results:
- None of the homozygous purinoceptor knockouts were developmentally lethal, suggesting functional compensation or limited roles in development.
- Gain or loss of function studies have identified several purinoceptors as potential therapeutic targets.
- Discrepancies between models highlighted differences in human and mouse gene structures and the critical role of the mouse genetic background.
Conclusions:
- Mouse models are indispensable for advancing the understanding of purinergic signaling and purinoceptor function.
- Genetic manipulation of purinoceptor genes in mice offers insights into therapeutic strategies.
- Careful consideration of mouse strain background is essential for accurate interpretation of purinoceptor research.
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