Analysis of the impact of CSF-1 administration in adult rats using a novel Csf1r-mApple reporter gene.

Abstract

Macrophages are present in large numbers in every tissue in the body where they play critical roles in development and homeostasis. They exhibit remarkable phenotypic and functional diversity, underpinning their adaptation to specialized roles in each tissue niche. CSF1, signaling through the CSF1 receptor, which is restricted to monocyte-macrophage lineage cells in adults, is a critical growth factor controlling macrophage proliferation, differentiation, and many aspects of mature macrophage function. We have generated a macrophage reporter rat, utilizing a construct containing elements of the mouse Csf1r promoter and the highly conserved Fms intronic regulatory element to drive mApple fluorescent protein expression. Csf1r-mApple was robustly expressed in monocyte-macrophage lineage cells in rat bone marrow (BM), peripheral blood, and tissues, with detectable expression in granulocytes and B cells and no evidence of expression in hematopoietic precursors or non-hematopoietic cells. Here, we use the Csf1r-mApple transgene to highlight and dissect the abundance and heterogeneity of rat tissue macrophage populations, and to demonstrate parallel increases in blood monocytes and multiple tissue macrophage populations, including BM, liver, spleen, and lung, in response to CSF1 treatment in vivo. The Csf1r-mApple rat is a novel tool enabling analysis of rat macrophages in situ by direct imaging and providing an additional phenotypic marker to facilitate exploration of rat tissue macrophage phenotypic and functional heterogeneity.