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

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

Research output: Contribution to journalArticle

131 Citations (Scopus)

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
StatePublished - Oct 15 1998
Externally publishedYes

Fingerprint

Protein C
Anticoagulants
Protein C Deficiency
Proteins
Fibrinogen
Hemorrhage
Intracranial Thrombosis
Liver
Brain
Gene Silencing
Fibrin
Embryonic Development
Blood Vessels
Thrombosis
Necrosis
Alleles
Genotype
Parturition
Pathology

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jalbert, L. R., Rosen, E., Moons, L., Chan, J. C. Y., Carmeliet, P., Collen, D., & Castellino, F. J. (1998). Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice. Journal of Clinical Investigation, 102(8), 1481-1488.

Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice. / Jalbert, Louise R.; Rosen, Elliot; Moons, Lieve; Chan, Joyce C Y; Carmeliet, Peter; Collen, Désiré; Castellino, Francis J.

In: Journal of Clinical Investigation, Vol. 102, No. 8, 15.10.1998, p. 1481-1488.

Research output: Contribution to journalArticle

Jalbert, LR, Rosen, E, Moons, L, Chan, JCY, Carmeliet, P, Collen, D & Castellino, FJ 1998, 'Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice', Journal of Clinical Investigation, vol. 102, no. 8, pp. 1481-1488.
Jalbert, Louise R. ; Rosen, Elliot ; Moons, Lieve ; Chan, Joyce C Y ; Carmeliet, Peter ; Collen, Désiré ; Castellino, Francis J. / Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice. In: Journal of Clinical Investigation. 1998 ; Vol. 102, No. 8. pp. 1481-1488.
@article{67fe7e14bb1b4b5f9572cb7bf378b899,
title = "Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice",
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.",
keywords = "Coagulation, Embryonic development, Gene deletion, Inflammation, Protein C deficiency",
author = "Jalbert, {Louise R.} and Elliot Rosen and Lieve Moons and Chan, {Joyce C Y} and Peter Carmeliet and D{\'e}sir{\'e} Collen and Castellino, {Francis J.}",
year = "1998",
month = "10",
day = "15",
language = "English (US)",
volume = "102",
pages = "1481--1488",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "8",

}

TY - JOUR

T1 - Inactivation of the gene for anticoagulant protein C causes lethal perinatal consumptive coagulopathy in mice

AU - Jalbert, Louise R.

AU - Rosen, Elliot

AU - Moons, Lieve

AU - Chan, Joyce C Y

AU - Carmeliet, Peter

AU - Collen, Désiré

AU - Castellino, Francis J.

PY - 1998/10/15

Y1 - 1998/10/15

N2 - 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.

AB - 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.

KW - Coagulation

KW - Embryonic development

KW - Gene deletion

KW - Inflammation

KW - Protein C deficiency

UR - http://www.scopus.com/inward/record.url?scp=0032532678&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032532678&partnerID=8YFLogxK

M3 - Article

C2 - 9788960

AN - SCOPUS:0032532678

VL - 102

SP - 1481

EP - 1488

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 8

ER -