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Blood. 2014 Oct 9;124(15):e33-44. doi: 10.1182/blood-2014-04-568691. Epub 2014 Jul 16.

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.

Author information

1
Sir William Dunn School of Pathology, University of Oxford, United Kingdom;
2
Division of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom;
3
Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom;
4
Genentech, South San Francisco, CA;
5
Jenner Institute, University of Oxford, Oxford, United Kingdom; and.
6
Cardiovascular Research Institute, Departments of Physiology and Medicine, University of California San Francisco, CA.

Abstract

The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX3CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation.

Comment in

PMID:
25030063
PMCID:
PMC4192756
DOI:
10.1182/blood-2014-04-568691
[Indexed for MEDLINE]
Free PMC Article
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