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Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
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Alternatively spliced tissue factor is not sufficient for embryonic development.

Susanna H M Sluka1, Alexander Akhmedov1, Johannes Vogel2

  • 1Cardiovascular Research, Institute of Physiology, University of Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

Plos One
|June 1, 2014
PubMed
Summary
This summary is machine-generated.

Soluble alternatively-spliced tissue factor (asTF) does not support embryonic yolk sac vasculature integrity or survival. In mice lacking full-length tissue factor (flTF), asTF lacks procoagulant activity and fails to maintain vascular function.

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Area of Science:

  • Developmental Biology
  • Hematology
  • Molecular Biology

Background:

  • Tissue factor (TF) initiates blood coagulation and exists as two mRNA splice isoforms: full-length TF (flTF) and alternatively-spliced TF (asTF).
  • Complete TF knockout in mice leads to embryonic lethality due to yolk sac vasculature failure.
  • The role of asTF in embryonic development, particularly in vascular integrity and coagulation, remains unclear.

Purpose of the Study:

  • To investigate the function of soluble alternatively-spliced tissue factor (asTF) during embryonic development in the absence of full-length tissue factor (flTF).
  • To determine if asTF possesses procoagulant activity or contributes to embryonic yolk sac vascular stability through non-coagulant mechanisms.

Main Methods:

  • Generation of homozygous asTF knock-in (asTFKI) mice expressing only asTF.
  • Analysis of embryonic lethality, yolk sac vasculature development, and protein expression in asTFKI embryos.
  • Assessment of procoagulant activity using plasma clotting assays.

Main Results:

  • asTFKI mice exhibited embryonic lethality between days 9.5 and 10.5.
  • asTF protein was expressed in asTFKI embryos, but no procoagulant activity was detected.
  • Yolk sac vasculature in asTFKI embryos showed progressive erythrocyte loss and disintegration by day 10.5, despite normal initial development of mesodermal layers and blood islands.

Conclusions:

  • Embryonic asTF lacks measurable procoagulant activity.
  • asTF does not support embryonic yolk sac vessel stability via non-coagulant mechanisms.
  • The absence of flTF and the lack of functional asTF result in failure to maintain embryonic vasculature and survival.