A new genetic strategy for targeting microglia in development and disease

Elife. 2020 Jun 23:9:e54590. doi: 10.7554/eLife.54590.

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 neuroinflammation. 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.

Keywords: fate mapping; immunology; inflammation; microglia; mouse; multiple sclerosis; neuroinflammation; neuroscience; ribosomal profiling; stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / pathology
  • Embryo, Mammalian / anatomy & histology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Knock-In Techniques / methods*
  • Immunoprecipitation
  • Inflammation / pathology
  • Mice
  • Microglia / pathology
  • Microglia / physiology*
  • Receptors, Purinergic P2Y12 / genetics
  • Receptors, Purinergic P2Y12 / metabolism
  • Recombinant Proteins

Substances

  • P2ry12 protein, mouse
  • Receptors, Purinergic P2Y12
  • Recombinant Proteins

Associated data

  • GEO/GSE138333
  • GEO/GSE114001