1. Immunology and Inflammation
  2. Neuroscience

A new genetic strategy for targeting microglia in development and disease

  1. Gabriel L McKinsey  Is a corresponding author
  2. Carlos O Lizama
  3. Amber E Keown-Lang
  4. Abraham Niu
  5. Nicolas Santander
  6. Amara Larpthaveesarp
  7. Elin Chee
  8. Fernando F Gonzalez
  9. Thomas D Arnold  Is a corresponding author
  1. University of California, San Francisco, United States
https://doi.org/10.7554/eLife.54590
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Cite this article
  1. Gabriel L McKinsey
  2. Carlos O Lizama
  3. Amber E Keown-Lang
  4. Abraham Niu
  5. Nicolas Santander
  6. Amara Larpthaveesarp
  7. Elin Chee
  8. Fernando F Gonzalez
  9. Thomas D Arnold
(2020)
A new genetic strategy for targeting microglia in development and disease
eLife 9:e54590.
https://doi.org/10.7554/eLife.54590
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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
The following previously published data sets were used

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5503-2830

  2. Carlos O Lizama

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Amber E Keown-Lang

    Pediatrics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Abraham Niu

    Pediatrics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Nicolas Santander

    Pediatrics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8919-833X

  6. Amara Larpthaveesarp

    Pediatrics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Elin Chee

    Pediatrics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Fernando F Gonzalez

    Pediatrics, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. 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.

Reviewing Editor

  1. 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

  1. Received: December 19, 2019
  2. Accepted: June 23, 2020
  3. Accepted Manuscript published: June 23, 2020 (version 1)
  4. Accepted Manuscript updated: June 25, 2020 (version 2)
  5. 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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  1. Gabriel L McKinsey
  2. Carlos O Lizama
  3. Amber E Keown-Lang
  4. Abraham Niu
  5. Nicolas Santander
  6. Amara Larpthaveesarp
  7. Elin Chee
  8. Fernando F Gonzalez
  9. Thomas D Arnold
(2020)
A new genetic strategy for targeting microglia in development and disease
eLife 9:e54590.
https://doi.org/10.7554/eLife.54590

Share this article

https://doi.org/10.7554/eLife.54590

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