Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice.

Abstract:

:Utilizing both the TET-OFF and TET-ON systems in combination with transcriptional control elements of the Tie-2 gene, we have established a series of transgenic activator and responder mice for TET-regulated endothelial cell-specific transgene expression in double transgenic mouse embryos and in adult mice. TET-regulated expression of LacZ reporter genes could be achieved in virtually all endothelia in mid gestation stage mouse embryos. In contrast in adult mice, using the very same Tie-2 tTA activator mouse strain, we observed striking differences of TET-induced gene expression from various inducible expression constructs in different vascular beds. Non-endothelial expression was never detected. The prominent differences in completeness of TET-induced endothelial expression highlight the still underestimated critical role of the responder mouse lines for uniform TET-induced gene expression in heterogeneous cell populations such as endothelial cells. Interestingly, in double transgenic mice inducibly expressing several different adhesion molecules, no adverse effects were observed even though these proteins were robustly expressed on endothelial cells in adult tissues. These transgenic model systems provide versatile tools for the TET-regulated manipulation of endothelial cell-specific gene expression in the entire embryonic vasculature and distinct vascular beds in adult mice.

journal_name

Exp Cell Res

authors

Deutsch U,Schlaeger TM,Dehouck B,Döring A,Tauber S,Risau W,Engelhardt B

doi

10.1016/j.yexcr.2007.12.026

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

1202-16

issue

6

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(08)00003-7

journal_volume

314

pub_type

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