Case report: promoter activity may define the alveolar macrophage dichotomy.

Cre-LoxP system has been widely used to induce recombination of floxed genes of interest. Currently available macrophage promoter-specific Cre recombinase mice strains have various limitations that warrants the testing of additional Cre strains. V-maf usculoponeurotic ibrosarcoma oncogene family, protein - () mice label macrophages in most organs such as spleen, small intestine, lung, bone marrow, and peritoneal cavity. However, whether recombinase targets the gene recombination in alveolar macrophage remains untested. Here, we utilized strain that expresses mTOM protein in all the cells of mouse body except for those that express -Cre-regulated mEGFP. We performed fluorescent microscopy and flow cytometry to analyze mTOM and mEGFP expression in alveolar macrophages from mice. Our analyses revealed that the -Cre is active in only ~40% of the alveolar macrophages in an age-independent manner. While - (mTOM+/mEGFP-) and + (mEGFP+) alveolar macrophages exhibit comparable expression of CD11b and CD11c surface markers, the surface expression of MHCII is elevated in the + (mEGFP+) macrophages. The bone marrow-derived macrophages from mice are highly amenable to Cre-LoxP recombination The bone marrow depletion and reconstitution experiment revealed that ~98% of alveolar macrophages from → WT chimera are amenable to the -Cre-mediated recombination. Finally, the stimulation and ozone exposure to the mice promote the -Cre-mediated recombination in alveolar macrophages. In conclusion, while the -/+ dichotomy thwarts the use of for the induction of floxed alleles in the entire alveolar macrophage population, this strain provides a unique tool to induce gene deletion in alveolar macrophages that encounter microenvironment in the lung airspaces.