Zhang N, Fang Z, Contag PR, Purchio AF, West DB, et al.
Blood. Date of publication 2004 Jan 15;volume 103(2):617-26.
1. Blood. 2004 Jan 15;103(2):617-26. Epub 2003 Sep 25.
Tracking angiogenesis induced by skin wounding and contact hypersensitivity using
a Vegfr2-luciferase transgenic mouse.
Zhang N(1), Fang Z, Contag PR, Purchio AF, West DB.
Author information:
(1)Xenogen Corporation, 860 Atlantic Ave, Alameda, CA 94501.
ning.zhang@xenogen.com
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.
DOI: 10.1182/blood-2003-06-1820
PMID: 14512298 [Indexed for MEDLINE]
