A mouse model of microglia-specific ablation in the embryonic central nervous system

Chenmin Li; Hiroyuki Konishi; Kimitoshi Nishiwaki; Katsuaki Sato; Takaki Miyata; Hiroshi Kiyama

doi:10.1016/j.neures.2021.06.002

A mouse model of microglia-specific ablation in the embryonic central nervous system

Neurosci Res. 2021 Dec:173:54-61. doi: 10.1016/j.neures.2021.06.002. Epub 2021 Jun 23.

Authors

Chenmin Li¹, Hiroyuki Konishi², Kimitoshi Nishiwaki³, Katsuaki Sato⁴, Takaki Miyata⁵, Hiroshi Kiyama⁶

Affiliations

¹ Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
² Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. Electronic address: konishi@med.nagoya-u.ac.jp.
³ Department of Anesthesiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
⁴ Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, 889-1692, Japan.
⁵ Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
⁶ Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. Electronic address: kiyama@med.nagoya-u.ac.jp.

PMID: 34157360
DOI: 10.1016/j.neures.2021.06.002

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 Siglech^dtr 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.

Keywords: Depletion; Development; Diphtheria toxin; Embryo; In utero; Macrophage.

MeSH terms

Animals
Central Nervous System*
Disease Models, Animal
Embryo, Mammalian
Macrophages
Mice
Microglia*