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.

小胶质细胞在早期胚胎阶段迁移到中枢神经系统 (CNS)，被认为在 CNS 发育中发挥着各种作用。然而，它们在胚胎中的作用在很大程度上是未知的，部分原因是胚胎中缺乏有效的小胶质细胞消融系统。在这里，我们通过将白喉毒素 (DT) 注射到Siglech ^dtr小鼠的羊水中来展示小胶质细胞消融模型，其中编码 DT 受体的基因被敲入小胶质细胞特异性基因位点Siglech. 我们发现胚胎小胶质细胞在整个中枢神经系统中耗尽了几天，包括一些小胶质细胞短暂积累的区域，在胚胎第 10.5 天的任何胚胎时间点，当小胶质细胞在中枢神经系统中定殖时。该消融系统对小胶质细胞具有特异性，因为 CNS 相关巨噬细胞与位于脑膜等 CNS 界面的小胶质细胞不同，不受影响。因此，该小胶质细胞消融系统对于研究小胶质细胞的胚胎功能非常有效。