Abstract |
The genes that regulate the formation of blood vessels in adult tissues represent promising therapeutic targets because angiogenesis plays a role in many diseases, including cancer. We wished to develop a mouse model allowing characterization of gene function in adult angiogenic vasculature while minimizing effects on embryonic vasculature or adult quiescent vasculature. Here we describe a transgenic mouse model that allows expression of proteins in the endothelial cells of newly forming blood vessels in the adult using a selective retroviral gene delivery system. We generated transgenic mouse lines that express the TVA receptor for the RCAS avian-specific retrovirus from Flk1 gene regulatory elements that drive expression in proliferating endothelial cells. Several of these Flk1-TVA lines expressed TVA mRNA in the embryonic vasculature and TVA protein in new blood vessels growing into subcutaneous extracellular matrix implants in adult mice. In a Flk1-TVA line that was crossed with the MMTV-PyMT transgenic mammary tumor model, tumor endothelial cells also expressed the TVA protein. Furthermore, endothelial cells in extracellular matrix implants and the tumors of Flk1-TVA mice were susceptible to RCAS infection, as determined by expression of green fluorescent protein encoded by the virus. The Flk1-TVA mouse model in conjunction with the RCAS gene delivery system will be useful to study molecular mechanisms underlying adult forms of angiogenesis.
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Authors | Virginie S Vervoort, Mark Lu, Fatima Valencia, Jacqueline Lesperance, Georg Breier, Robert Oshima, Elena B Pasquale |
Journal | Transgenic research
(Transgenic Res)
Vol. 17
Issue 3
Pg. 403-15
(Jun 2008)
ISSN: 0962-8819 [Print] Netherlands |
PMID | 18027100
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Avian Proteins
- Receptors, Virus
- Tva receptor
- Vascular Endothelial Growth Factor Receptor-2
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Topics |
- Alpharetrovirus
(genetics)
- Animals
- Avian Proteins
(genetics)
- Blood Vessels
(metabolism)
- Cells, Cultured
- Cloning, Molecular
- Disease Susceptibility
- Embryo, Mammalian
- Female
- Gene Expression Regulation, Developmental
- Gene Transfer Techniques
- Humans
- Mice
- Mice, Transgenic
- Models, Biological
- Neovascularization, Physiologic
(genetics)
- Receptors, Virus
(genetics)
- Retroviridae Infections
(genetics)
- Terminal Repeat Sequences
(genetics)
- Transgenes
- Vascular Endothelial Growth Factor Receptor-2
(genetics)
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