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Updated: Nov 1, 2025
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
A mouse model of microglia-specific ablation in the embryonic central nervous system
Chenmin Li1, Hiroyuki Konishi1, Kimitoshi Nishiwaki2
1Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Abstract:
Microglia, which migrate into the central nervous system (CNS) during the early embryonic stages, are considered to play various roles in CNS development. However, their embryonic roles are largely unknown, partly due to the lack of an effective microglial ablation system in the embryo. Here, we show a microglial ablation model by injecting diphtheria toxin (DT) into the amniotic fluid of Siglechdtr mice, in which the gene encoding DT receptor is knocked into the microglia-specific gene locus Siglech. We revealed that embryonic microglia were depleted for several days throughout the CNS, including some regions where microglia transiently accumulated, at any embryonic time point from embryonic day 10.5, when microglia colonize the CNS. This ablation system was specific for microglia because CNS-associated macrophages, which are a distinct population from microglia that reside in the CNS interfaces such as meninges, were unaffected. Therefore, this microglial ablation system is highly effective for studying the embryonic functions of microglia.
Insights
Researchers developed a novel method to deplete embryonic microglia in mice using diphtheria toxin. This technique allows for the study of microglia's crucial roles in central nervous system development.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia are key immune cells in the central nervous system (CNS).
- Their roles during embryonic CNS development are largely unknown.
- Existing methods lack effective embryonic microglial ablation.
Purpose of the Study:
- To establish an effective method for ablating embryonic microglia.
- To enable the study of microglia-dependent CNS development.
Main Methods:
- Developed a microglial ablation model in Siglechdtr mice.
- Administered diphtheria toxin (DT) via amniotic fluid injection.
- Utilized microglia-specific Siglech gene locus for DT receptor insertion.
Main Results:
- Successfully depleted embryonic microglia throughout the CNS for several days.
- Ablation was effective from embryonic day 10.5 onwards.
- The system specifically targeted microglia, sparing CNS-associated macrophages.
Conclusions:
- The developed DT-based system is highly effective for embryonic microglial ablation.
- This model provides a powerful tool to investigate the embryonic functions of microglia.
- Enables future research into microglia's impact on CNS development.
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