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Inducible and selective transgene expression in murine vascular endothelium

¹ Millennium Pharmaceuticals, South San Francisco 94080
² Division of Cardiovascular Medicine, Stanford University Hospital and Clinics, Stanford, California 94305

We have developed a system utilizing the murine Tie2 promoter/enhancer coupled with the "tetracycline-on" regulatory elements to create a model that allows regulated and selective expression of a ß-galactosidase (ßGal) reporter transgene in the adult murine vascular endothelium. Two independent lines of viable and fertile mice were characterized, and they exhibit minimal ßGal expression under basal conditions. In response to exogenous doxycycline (Dox), selective expression of ßGal was demonstrated in the vascular endothelium of all tissues examined. En face analyses of the aorta and its principle branches indicate that the vast majority of lumenal endothelial cells express the transgene. Inducible ßGal expression also extends to the endocardium and the microvasculature of all organs. There is no evidence of specific transgene expression in nonendothelial cell types. Induction of the ßGal was effectively achieved after 3 days of oral Dox treatment and persisted for over 3 mo with continuous administration. This model can now be widely applied to study the role of specific genes in the phenotype of adult murine vasculature.

transgenic mice; Tie2; tetracycline regulation system; gene expression; vascular biology

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