title: Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.
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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, United Kingdom;
authors.forename: Asif J
authors.initials: AJ
authors.lastname: Iqbal
authors.affiliation: 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;
authors.forename: Eileen
authors.initials: E
authors.lastname: McNeill
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, United Kingdom;
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Kapellos
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, United Kingdom;
authors.forename: Daniel
authors.initials: D
authors.lastname: Regan-Komito
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom;
authors.forename: Sophie
authors.initials: S
authors.lastname: Norman
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, United Kingdom;
authors.forename: Sarah
authors.initials: S
authors.lastname: Burd
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom;
authors.forename: Nicola
authors.initials: N
authors.lastname: Smart
authors.affiliation: Genentech, South San Francisco, CA;
authors.forename: Daniel E W
authors.initials: DE
authors.lastname: Machemer
authors.affiliation: Jenner Institute, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Elena
authors.initials: E
authors.lastname: Stylianou
authors.affiliation: Jenner Institute, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.affiliation: 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;
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
authors.affiliation: Cardiovascular Research Institute, Departments of Physiology and Medicine, University of California San Francisco, CA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, United Kingdom;
authors.forename: David R
authors.initials: DR
authors.lastname: Greaves
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002454:Cell Differentiation; D002908:Chronic Disease; D047108:Embryonic Development; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology*; D009164:Mycobacterium Infections / Q000473:pathology; D009163:Mycobacterium bovis / Q000502:physiology; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000073883:CX3C Chemokine Receptor 1; D049452:Green Fluorescent Proteins; D019707:Receptors, Chemokine; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C471885:Cx3cr1 protein, mouse