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Prothrombin deficiency results in embryonic and neonatal lethality in mice

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • W Y Sun
  • D P Witte
  • J L Degen
  • M C Colbert
  • M C Burkart
  • K Holmbäck
  • Q Xiao
  • T H Bugge
  • S J Degen

The conversion of prothrombin (FII) to the serine protease, thrombin (FIIa), is a key step in the coagulation cascade because FIIa triggers platelet activation, converts fibrinogen to fibrin, and activates regulatory pathways that both promote and ultimately suppress coagulation. However, several observations suggest that FII may serve a broader physiological role than simply stemming blood loss, including the identification of multiple G protein-coupled, thrombin-activated receptors, and the well-documented mitogenic activity of FIIa in in vitro test systems. To explore in greater detail the physiological roles of FII in vivo, FII-deficient (FII-/-) mice were generated. Inactivation of the FII gene leads to partial embryonic lethality with more than one-half of the FII-/- embryos dying between embryonic days 9.5 and 11.5. Bleeding into the yolk sac cavity and varying degrees of tissue necrosis were observed in many FII-/- embryos within this gestational time frame. However, at least one-quarter of the FII-/- mice survived to term, but ultimately they, too, developed fatal hemorrhagic events and died within a few days of birth. This study directly demonstrates that FII is important in maintaining vascular integrity during development as well as postnatal life.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind95
Udgave nummer13
Sider (fra-til)7597-602
Antal sider6
ISSN0027-8424
StatusUdgivet - 23 jun. 1998

ID: 201190248