A new genetic strategy for targeting microglia in development and disease

Abstract
Data availability
Article and author information
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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.

The following data sets were generated

(2020) Translational profiling of microglia
NCBI Gene Expression Omnibus, GSE138333.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE138333

The following previously published data sets were used

1. Haimon Z
2. Volaski A
3. Orthgiess J
4. Boura-Halfon S
5. Varol D
6. Shemer A
7. Yona S
8. Zuckerman B
9. David E
10. Chappell-Maor L
11. Bechmann I
12. Gericke M
13. Ulitsky I
14. Jung S
(2018) Re-evaluating Microglia Expression Profiles Using RiboTag and Cell Isolation Strategies
NCBI Gene Expression Omnibus, GSE114001.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE114001

Article and author information

Author details

Gabriel L McKinsey

Pediatrics, University of California, San Francisco, San Francisco, United States

For correspondence
gabriel.mckinsey@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5503-2830
Carlos O Lizama

Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Amber E Keown-Lang

Pediatrics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Abraham Niu

Pediatrics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Nicolas Santander

Pediatrics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8919-833X
Amara Larpthaveesarp

Pediatrics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Elin Chee

Pediatrics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Fernando F Gonzalez

Pediatrics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Thomas D Arnold

Pediatrics, University of California, San Francisco, San Francisco, United States

For correspondence
thomas.arnold@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

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.

Ethics

Animal experimentation: All mouse work was performed in accordance with UCSF Institutional Animal Care and Use Committee protocols (#AN177934-01).

Copyright

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.