Transgene

Recombinase

Gene

Cre recombinase

Phenotype

Genetically modified mouse

Cell

Recombination

Conditional gene knockout

Complementation

Cell type

Progenitor cell

In vitro

Immunology

Inflammation

Macrophage

Microglia

Stem cell

Reproductive biology

Genetics

Fate mapping

Transgenesis

Biology

Embryogenesis

Cell biology

Immunity

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: Sall1ncre: Cx3cr1ccre mice specifically target parenchymal microglia and compound transgenic Lyve1ncre: Cx3cr1ccre 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.

A Binary Cre Transgenic Approach Dissects Microglia and CNS Border-Associated Macrophages