A new genetic strategy for targeting microglia in development and disease
Abstract
As the resident macrophages of the brain and spinal cord, microglia are crucial for the phagocytosis of infectious agents, apoptotic cells and synapses. During brain injury or infection, bone-marrow derived macrophages invade neural tissue, making it difficult to distinguish between invading macrophages and resident microglia. In addition to circulation-derived monocytes, other non-microglial central nervous system (CNS) macrophage subtypes include border-associated meningeal, perivascular and choroid plexus macrophages. Using immunofluorescent labeling, flow cytometry and Cre-dependent ribosomal immunoprecipitations, we describe P2ry12-CreER, a new tool for the genetic targeting of microglia. We use this new tool to track microglia during embryonic development and in the context of ischemic injury and neuro-inflammation. Because of the specificity and robustness of microglial recombination with P2ry12-CreER, we believe that this new mouse line will be particularly useful for future studies of microglial function in development and disease.
Data availability
Sequencing data have been submitted to the Gene Expression Omnibus (GEO) repository for datasets. The accession number for this dataset is: GSE138333.
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Translational profiling of microgliaNCBI Gene Expression Omnibus, GSE138333.
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Re-evaluating Microglia Expression Profiles Using RiboTag and Cell Isolation StrategiesNCBI Gene Expression Omnibus, GSE114001.
Article and author information
Author details
Funding
National Institutes of Health (K08NS96192)
- Thomas D Arnold
American Heart Association (20POST35120371)
- Nicolas Santander
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Isaac M Chiu, Harvard Medical School, United States
Ethics
Animal experimentation: All mouse work was performed in accordance with UCSF Institutional Animal Care and Use Committee protocols (#AN177934-01).
Version history
- Received: December 19, 2019
- Accepted: June 23, 2020
- Accepted Manuscript published: June 23, 2020 (version 1)
- Accepted Manuscript updated: June 25, 2020 (version 2)
- Version of Record published: July 22, 2020 (version 3)
Copyright
© 2020, McKinsey et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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