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Publication : A novel Flk1-TVA transgenic mouse model for gene delivery to angiogenic vasculature.

First Author  Vervoort VS Year  2008
Journal  Transgenic Res Volume  17
Issue  3 Pages  403-15
PubMed ID  18027100 Mgi Jnum  J:134089
Mgi Id  MGI:3784940 Doi  10.1007/s11248-007-9156-1
Citation  Vervoort VS, et al. (2008) A novel Flk1-TVA transgenic mouse model for gene delivery to angiogenic vasculature. Transgenic Res 17(3):403-15
abstractText  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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