Disease relevance of Procr

• Procr heterozygosity results in a mild increase of thrombosis tendency and little influence on the response to endotoxin [1].
• Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice [1].

High impact information on Procr

• In these studies, thrombin infusion experiments revealed that EPCR heterozygosity (Procr(+/-)) impaired protein C activation by approximately 30% [1].
• Challenge of the Procr(+/-) mice with lipopolysaccharide (LPS) did not significantly exaggerate their response compared with wild-type mice [1].
• The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood vessels and by hematopoietic stem cells [2].
• 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 [3].
• These findings show that extraembryonic EPCR expression is critical for embryo development [3].

Biological context of Procr

• These data further show that minimal levels of EPCR are able to support male and female virility, as well as embryonic development, birth, and survival to adulthood [4].
• The nucleotide sequence of the entire gene encoding the murine endothelial cell receptor for activated protein C (EPCR) has been determined [5].
• From the locations of the introns in this gene and analysis of the exon structures, it is clear the EPCR gene is a member of the CD1 class of multiple histocompatibility proteins. and its cDNA sequence is nearly identical to that of CCD41, a centrosome-associated protein [5].
• Replacing amino acids from residue 193 to residue 200 with the FLAG(TM) sequence (DYKDDDDK) completely blocks EPCR shedding, whereas a single amino acid substitution in this region has less effect on EPCR shedding [6].
• SUMMARY: The emerging clinical evidence of endothelial cell protein C receptor involvement in thrombotic disease suggests that the understanding of endothelial cell protein C receptor genotype and the knowledge of auto-antibodies may aid in diagnosing the risk of thrombotic events in patients [7].

Anatomical context of Procr

• Immunohistochemistry revealed the lack of EPCR in trophoblast giant cells of EPCR(-/-) embryos [8].
• To determine the physiological importance of EPCR, we generated EPCR-deficient mice by homologous targeting in embryonic stem cells [8].
• EPCR(-/-) embryos removed from extra-embryonic membranes and tissues at day E7.5 and cultured in vitro developed beyond E10.5, suggesting a role for EPCR in the normal function of the placenta and/or at the materno-embryonic interface [8].
• In the embryo, EPCR was weakly detected in aortic endothelial cells from E13 [9].
• 5. Thereafter, EPCR levels increased in certain large blood vessels endothelial cells suggesting that the specificity of EPCR to large vessels is conferred in utero [9].

Analytical, diagnostic and therapeutic context of Procr

• Despite the retention of the entire endogenous EPCR coding sequence in the altered EPCR gene locus, only very low EPCR message contents were detected in mice by quantitative RT-PCR during embryogenesis and up to at least early adulthood [4].

References