Tracking angiogenesis induced by skin wounding and contact hypersensitivity using a Vegfr2-luciferase transgenic mouse

• Published in: Blood Vol. 103; no. 2; pp. 617 - 626
• Main Authors: Zhang, Ning, Fang, Zuxu, Contag, Pamela R., Purchio, Anthony F., West, David B.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.01.2004; The Americain Society of Hematology
• Subjects: Animals; Aorta; Base Sequence; Biological and medical sciences; Cattle; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells, Cultured; Dexamethasone - pharmacology; DNA Primers; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Gene Library; Genes, Reporter; Kinetics; Luciferases - genetics; Luciferases - metabolism; Mice; Mice, Transgenic; Molecular and cellular biology; Neovascularization, Physiologic - physiology; Polymerase Chain Reaction; Promoter Regions, Genetic; Recombinant Fusion Proteins - metabolism; Skin - drug effects; Skin - injuries; Skin - pathology; Time Factors; Transfection; Vascular Endothelial Growth Factor Receptor-2 - genetics; Wound Healing - drug effects; Wound Healing - physiology; Animal model; Cypridina-luciferin 2-monooxygenase; EC 1.13.12.5; Enzyme; Transcription promoter; Luciferase; Rodentia; EC 1.13.12.6; Transgenic animal; Gene expression; Angiogenesis; Vertebrata; Mammalia; Mouse; Skin; Oxidoreductases; Renilla-luciferin 2-monooxygenase; Vascular endothelial growth factor receptor 2; Cicatrization; Contact hypersensitivity
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-06-1820

The vascular endothelial growth factor-2 (VEGFR2) gene is transcriptionally regulated during angiogenesis. The ability to monitor and quantify VEGFR2 expression in vivo may facilitate a better understanding of the role of VEGFR2 in different states. Here we describe a transgenic mouse, Vegfr2-luc, in which a luciferase reporter is under control of the murine VEGFR2 promoter. In adult mice, luciferase activity was highest in lung and uterus, intermediate in heart, skin, and kidney, and lower in other tissues. Luciferase expression in these tissues correlated with endogenous VEGFR2 mRNA expression. In a cutaneous wound-healing model, Vegfr2-luc expression was induced in the wound tissue. Histologic and immunohistochemical studies showed significant macrophage infiltration into the wound and induction of Vegfr2-luc expression in endothelial and stromal cells. Dexamethasone significantly suppressed Vegfr2-luc expression and macrophage infiltration into the wound, resulting in delayed healing and impaired angiogenesis. In a skin hypersensitivity reaction produced by treatment with oxazolone, Vegfr2-luc expression was induced in the ear. Treatment by dexamethasone markedly suppressed Vegfr2-luc expression and leukocyte infiltration in the ear and was correlated with reduced dermal edema and epidermal hyperplasia. The Vegfr2-luc model will be valuable in monitoring the ability of drugs to affect angiogenesis in vivo.