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

Deutsch, Urban; Schlaeger, Thorsten M; Dehouck, Bénédicte; Döring, Axinia; Tauber, Silke; Risau, Werner; Engelhardt, Britta (2008). Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice. Experimental cell research, 314(6), pp. 1202-16. San Diego, Calif.: Elsevier 10.1016/j.yexcr.2007.12.026

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban; Döring, Axinia Samantha and Engelhardt, Britta

ISSN:

0014-4827

ISBN:

18272150

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

04 May 2014 23:16

Publisher DOI:

10.1016/j.yexcr.2007.12.026

PubMed ID:

18272150

Web of Science ID:

000254612700002

URI:

https://boris.unibe.ch/id/eprint/23659 (FactScience: 43322)

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