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 Resjournal_title
Experimental cell researchauthors
Deutsch U,Schlaeger TM,Dehouck B,Döring A,Tauber S,Risau W,Engelhardt Bdoi
10.1016/j.yexcr.2007.12.026subject
Has Abstractpub_date
2008-04-01 00:00:00pages
1202-16issue
6eissn
0014-4827issn
1090-2422pii
S0014-4827(08)00003-7journal_volume
314pub_type
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