Extraembryonic expression of EPCR is essential for embryonic viability.

Abstract:

:The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombin-thrombomodulin complex. Deletion of the EPCR gene (Procr) in mice leads to embryonic lethality before embryonic day 10 (E10.0). EPCR is detected in the giant trophoblast cells at the feto-maternal boundary from E7.5 and weakly in embryonic aortic endothelial cells from E13.5, suggesting that extraembryonic EPCR expression may be essential for embryonic viability. Using conditional knock-out strategies, we demonstrate that Procr-deficient embryos with EPCR expression on placenta giant trophoblasts can be carried to term and then develop normally. Conversely, EPCR expression in the embryo, without expression in the giant trophoblast cells, does not rescue the mice. In genetically modified mice with low tissue factor activity, Procr deficiency is not lethal to the embryo. As adults, Procr-deficient mice generate more thrombin and activate less protein C in response to procoagulant stimuli. Spontaneous thrombin formation in the deficient animals increases with age. These findings show that extraembryonic EPCR expression is critical for embryo development.

journal_name

Blood

journal_title

Blood

authors

Li W,Zheng X,Gu JM,Ferrell GL,Brady M,Esmon NL,Esmon CT

doi

10.1182/blood-2005-01-0406

subject

Has Abstract

pub_date

2005-10-15 00:00:00

pages

2716-22

issue

8

eissn

0006-4971

issn

1528-0020

pii

2005-01-0406

journal_volume

106

pub_type

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