Microglia are macrophages resident in the central nervous system. C-X3-C motif chemokine receptor 1 (CX3CR1) is a Gαi-coupled seven-transmembrane protein exclusively expressed in the mononuclear phagocyte system including microglia, as well as intestinal and kidney macrophages. Cx3cr1CreERT2 mice express Cre recombinase in a tamoxifen-inducible manner and have been widely used to delete target genes in microglia, since microglia are long-lived cells and outlive peripheral macrophages, which continuously turn over and lose their gene modification over time. ATG7 is an E1-like enzyme that plays an essential role in two ubiquitin-like reactions, ATG12-ATG5 conjugation and LC3-lipidation in autophagy. To study the role of ATG7 in adult microglia, we generated Cx3cr1CreERT2:Atg7fl/fl mice and deleted Atg7 at the age of 8 weeks, and found induction of intestinal adhesion. Since intestinal adhesion is caused by excessive inflammation, these results suggest that deletion of Atg7 in intestinal macrophages even for a short time results in inflammation that cannot be rescued by replenishment with wild-type intestinal macrophages. Our finding suggests that, depending on the roles of the gene, Cx3cr1-Cre-mediated gene deletion may yield unanticipated physiological outcomes outside the central nervous system, and careful necropsy is necessary to assure the microglia-specific roles of the target gene.

中文翻译：

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Cx3cr1CreERT2驱动的成年小鼠中的Atg7缺失诱导肠粘连。

小胶质细胞是驻留在中枢神经系统中的巨噬细胞。C-X3-C基序趋化因子受体1（CX3CR1）是Gαi偶联的七跨膜蛋白，仅在单核吞噬细胞系统（包括小胶质细胞）以及肠和肾巨噬细胞中表达。Cx3cr1CreERT2小鼠以他莫昔芬诱导的方式表达Cre重组酶，并已被广泛用于删除小胶质细胞中的靶基因，因为小胶质细胞是长寿的细胞，并且是外周巨噬细胞的存活期，随着时间的流逝，它们会不断翻身并失去其基因修饰。ATG7是一种E1样酶，在自噬中的两个泛素样反应（ATG12-ATG5偶联和LC3脂化）中起着至关重要的作用。为了研究ATG7在成年小胶质细胞中的作用，我们生成了Cx3cr1CreERT2：Atg7fl / fl小鼠，并在8周龄时删除了Atg7，并发现诱导肠粘连。由于肠粘连是由过度的炎症引起的，因此这些结果表明，即使在很短的时间内，肠巨噬细胞中Atg7的缺失也会导致炎症，而野生型肠巨噬细胞的补充不能挽救这种炎症。我们的发现表明，取决于基因的作用，Cx3cr1-Cre介导的基因缺失可能会在中枢神经系统外产生意想不到的生理结果，因此必须进行仔细的尸检以确保目标基因的小胶质细胞特异性作用。