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

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.
AuthorsVirginie S Vervoort, Mark Lu, Fatima Valencia, Jacqueline Lesperance, Georg Breier, Robert Oshima, Elena B Pasquale
JournalTransgenic research (Transgenic Res) Vol. 17 Issue 3 Pg. 403-15 (Jun 2008) ISSN: 0962-8819 [Print] Netherlands
PMID18027100 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Avian Proteins
  • Receptors, Virus
  • Tva receptor
  • Vascular Endothelial Growth Factor Receptor-2
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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