A Novel Role for Maternal Protein C in Embryonic Development
Abstract number: OR173
Lay13 AJ, Liang1,3 Z, Rosen1,3 ED, Castellino13 FJ
Anticoagulant Protein C (PC) is important not only for normal maintenance of hemostasis, but also for regulating host immune response during inflammation. Because mice with a designed total genetic deficiency for PC (PC-/-) die soon after birth, attempts to dissect PC function in various coagulation/inflammation-based pathologies has been limited to investigations with mice heterozygous for the PC deficiency. In this study, we generated mice expressing very low levels of PC (<12% of normal PC levels) using a novel transgenic strategy. These mice do not display the neonatal lethality of PC-/- mice, but spontaneously develop thrombosis and inflammation. The onset and severity of both phenotypes varies significantly, and is strongly dependent on plasma PC levels, suggesting that PC insufficiency is strongly correlated with poor survival. Our findings additionally provide the first direct evidence that maternal PC is vital for sustaining pregnancy beyond 7.5 days post-coitum (dpc), by regulating the balance of coagulation and inflammation during trophoblast invasion. These low PC transgenic mice provide a novel animal model to elucidate the importance of PC function in pregnancy-associated complications. The establishment of this mouse model will facilitate future research in many coagulation/inflammation-related pathologies where PC is implicated in the pathogenesis of the disease such as endotoxemia and sepsis.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2005; Volume 3, Supplement 1: abstract number
|Session name:||XXIst ISTH Congress|
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