Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice

Louise R. Jalbert, Elliot D. Rosen, Lieve Moons, Joyce C.Y. Chan, Peter Carmeliet, Désiré Collen, Francis J. Castellino

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

Matings of mice heterozygous for a protein C (PC) deficient allele, produced by targeted PC gene inactivation, yielded the expected Mendelian distribution of PC genotypes. Pups with a total deficiency of PC (PC(-/-)), obtained at embryonic day (E) 17.5 and at birth, appeared to develop normally macroscopically, but possessed obvious signs of bleeding and thrombosis and did not survive beyond 24 h after delivery. Microscopic examination of tissues and blood vessels of E17.5 PC(-/-) mice revealed their normal development, but scattered microvascular thrombosis in the brain combined with focal necrosis in the liver was observed. In addition, bleeding was noted in the brain near sites of fibrin deposition. The severity of these pathologies was exaggerated in PC(-/-) neonates. Plasma clottable fibrinogen was not detectable in coagulation assays in PC(-/-) neonatal mice, suggestive of fibrinogen depletion and secondary consumptive coagulopathy. Thus, while total PC deficiency did not affect the anatomic development of the embryo, severe perinatal consumptive coagulopathy occurred in the brain and liver of PC(-/-) mice, suggesting that a total PC deficiency is inconsistent with short-term survival.

Original languageEnglish (US)
Pages (from-to)1481-1488
Number of pages8
JournalJournal of Clinical Investigation
Volume102
Issue number8
DOIs
StatePublished - Oct 15 1998

Keywords

  • Coagulation
  • Embryonic development
  • Gene deletion
  • Inflammation
  • Protein C deficiency

ASJC Scopus subject areas

  • Medicine(all)

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