Targeting of transgene expression to the vascular endothelium of mice by homologous recombination at the thrombomodulin locus.

Abstract:

:We describe a straightforward gene-targeting technique to achieve uniform, stable, and genetically invariant expression of a transgene in the vascular endothelium of mice. To demonstrate the feasibility of this approach, the reporter gene bacterial beta-galactosidase was inserted via homologous recombination into the intronless thrombomodulin locus of murine embryonic stem cells. In this fashion, the lacZ gene is placed under the regulatory control of the endogenous thrombomodulin promoter. The expression of the transgene in adult mice recapitulated the widespread, stable, and high-level expression of the thrombomodulin gene in vascular endothelium. These data indicate that targeting of cDNAs into the thrombomodulin locus serves as a viable strategy to express transgenes in endothelial cells. Analysis of reporter gene expression revealed a heterogeneous pattern of thrombomodulin gene activity in the endothelium of the aorta and its tributaries. We also show that embryonic stem cells with a targeted thrombomodulin locus contribute in a mosaic fashion to the vascular endothelium of chimeric mice. This method for generating animals with a functionally heterogeneous cardiovascular system should provide an experimental technique for studying how localized genetic abnormalities in endothelial cell function lead to the development of vascular diseases.

journal_name

Circ Res

journal_title

Circulation research

authors

Weiler-Guettler H,Aird WC,Husain M,Rayburn H,Rosenberg RD

doi

10.1161/01.res.78.2.180

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

180-7

issue

2

eissn

0009-7330

issn

1524-4571

journal_volume

78

pub_type

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