The developmental and molecular heterogeneity of tissue macrophages is unravelling, as are their diverse contributions to physiology and pathophysiology. Moreover, also given tissues harbor macrophages in discrete anatomic locations. Functional contributions of specific cell populations can in mice be dissected using Cre recombinase-mediated mutagenesis. However, single promoter-based Cre models show limited specificity for cell types. Focusing on macrophages in the brain, we establish here a binary transgenic system involving complementation-competent NCre and CCre fragments whose expression is driven by distinct promoters: Sall1^ncre: Cx₃cr1^ccre mice specifically target parenchymal microglia and compound transgenic Lyve1^ncre: Cx₃cr1^ccre animals target vasculature-associated macrophages, in the brain, as well as other tissues. We imaged the respective cell populations and retrieved their specific translatomes using the RiboTag in order to define them and analyze their differential responses to a challenge. Collectively, we establish the value of binary transgenesis to dissect tissue macrophage compartments and their functions.

组织巨噬细胞的发育和分子异质性正在瓦解，它们对生理学和病理生理学的不同贡献也是如此。此外，还给定的组织在离散的解剖位置具有巨噬细胞。可以使用 Cre 重组酶介导的诱变在小鼠中解剖特定细胞群的功能贡献。然而，基于单个启动子的 Cre 模型对细胞类型的特异性有限。在大脑中着眼于巨噬细胞，我们在这里建立涉及互补能力的NCRE和CCRE片段其表达由不同的启动子驱动的转基因的二进制系统：SALL1 ^NCRE：CX ₃ CR1 ^CCRE小鼠特异性靶向实质小胶质细胞和转基因化合物LYVE1 ^NCRE：CX ₃ CR1 ^CCRE动物靶脉管系统相关巨噬细胞，在脑中，以及其他组织。我们对各自的细胞群进行成像并使用 RiboTag 检索它们的特定翻译组，以定义它们并分析它们对挑战的不同反应。总的来说，我们建立了二元转基因解剖组织巨噬细胞区室及其功能的价值。