In vivo detection of human vascular endothelial growth factor promoter activity in transgenic mouse skin

Jiro Kishimoto, Ritsuko Ehama, Yimin Ge, Takashi Kobayashi, Toshio Nishiyama, Michael Detmar, Robert E. Burgeson

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

We have generated transgenic mice expressing green fluorescent protein (GFP) driven by 2.453-kb (-2,362 to +91) of the 5'-upstream region of the human vascular endothelial growth factor (VEGF) promoter to monitor changes of VEGF gene transcription in situ. Neonatal transgenic mice exhibited GFP-derived fluorescence in tissues that have been previously reported to express VEGF mRNA expression, including lung, cartilage, and brain. In normal skin during postnatal development, moderate fluorescence was observed in the upper epidermis and, more prominently, in the outer root sheath keratinocytes of hair follicles. Strong upregulation of GFP fluorescence was observed in the hyperplastic epidermis of the wound edge at 48 hours after wounding, whereas little GFP fluorescence was detected in the dermis. In situ hybridization confirmed an identical expression pattern of VEGF mRNA in these wounds. Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced strong VEGF-GFP expression in suprabasal epidermis. Little or no fibroblast-derived fluorescence was seen both in the wound model and after TPA application. By confocal laser microscopy, increased GFP fluorescence was detectable in the epidermis of intact mouse ear skin as early as 6 hours after topical TPA treatment. Importantly, GFP fluorescence was also measurable in the skin of living transgenic mice. These results resolve the present controversy regarding the ability of VEGF-GFP transgenic mouse models to correctly reflect established patterns of VEGF expression, and show the model to be a powerful tool for the in vivo monitoring of VEGF gene expression.

Original languageEnglish (US)
Article number64522
Pages (from-to)103-110
Number of pages8
JournalAmerican Journal of Pathology
Volume157
Issue number1
DOIs
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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