Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice

Schlaeger, TM; Bartunkova, S; Lawitts, JA; Teichmann, G; Risau, W; Deutsch, U; Sato, TN (1997). Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 94(7), pp. 3058-63. Washington, D.C.: National Academy of Sciences NAS 10.1073/pnas.94.7.3058

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TIE2 is a vascular endothelial-specific receptor tyrosine kinase essential for the regulation of vascular network formation and remodeling. Previously, we have shown that the 1.2-kb 5' flanking region of the TIE2 promoter is capable of directing beta-galactosidase reporter gene expression specifically into a subset of endothelial cells (ECs) of transgenic mouse embryos. However, transgene activity was restricted to early embryonic stages and not detectable in adult mice. Herein we describe the identification and characterization of an autonomous endothelial-specific enhancer in the first intron of the mouse TIE2 gene. Furthermore, combination of the TIE2 promoter with an intron fragment containing this enhancer allows it to target reporter gene expression specifically and uniformly to virtually all vascular ECs throughout embryogenesis and adulthood. To our knowledge, this is the first time that an in vivo expression system has been assembled by which heterologous genes can be targeted exclusively to the ECs of the entire vasculature. This should be a valuable tool to address the function of genes during physiological and pathological processes of vascular ECs in vivo. Furthermore, we were able to identify a short region critical for enhancer function in vivo that contains putative binding sites for Ets-like transcription factors. This should, therefore, allow us to determine the molecular mechanisms underlying the vascular-EC-specific expression of the TIE2 gene.

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Deutsch, Urban

ISSN:

0027-8424

ISBN:

9096345

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1073/pnas.94.7.3058

PubMed ID:

9096345

Web of Science ID:

A1997WR93000057

URI:

https://boris.unibe.ch/id/eprint/22231 (FactScience: 32316)

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