A novel Flk1-TVA transgenic mouse model for gene delivery to angiogenic vasculature.
Transgenic Res
; 17(3): 403-15, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18027100
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Virais
/
Vasos Sanguíneos
/
Técnicas de Transferência de Genes
/
Transgenes
/
Proteínas Aviárias
/
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Transgenic Res
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos