Physiol. Genomics AJP: Renal Physiology
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Physiol. Genomics (September 11, 2002). doi:10.1152/physiolgenomics.00059.2002
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Articles in PresS, published online ahead of print September 11, 2002
Physiol Genomics, 10.1152/physiolgenomics.00059.2002
Submitted on May 10, 2002
Accepted on September 4, 2002

Inducible and Selective Transgene Expression in Murine Vascular Endothelium

Peter I Teng1, Maria R DiChiara2, Laszlo G Komuves2, Keith Abe2, Thomas Quertermous3, and James N Topper1*

1 Vascular Biology, Millennium Pharmaceuticals, Inc., South San Francisco, CA, USA; division of Cardiovascular Medicine, Stanford University Hospital and Clinics, Stanford, CA, USA
2 Vascular Biology, Millennium Pharmaceuticals, Inc., South San Francisco, CA, USA
3 division of Cardiovascular Medicine, Stanford University Hospital and Clinics, Stanford, CA, USA

* To whom correspondence should be addressed. E-mail: jamie.topper{at}mpi.com.

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 B-galactosidase (BGal) reporter transgene in the adult murine vascular endothelium. Two independent lines of viable and fertile mice were characterized, and they exhibit minimal BGal expression under basal conditions. In response to exogenous doxycycline, selective expression of BGal 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 BGal expression also extends to the endocardium and the microvasculature of all organs. There is no evidence of specific transgene expression in non-endothelial cell types. Induction of the BGal was effectively achieved after 3 days of oral doxycycline treatment and persisted for over 3 months with continuous administration. This model can now be widely applied to study the role of specific genes in the phenotype of the adult murine vasculature.




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