The characterization of mice with a targeted combined deficiency of protein C and factor XI

J. C Y Chan, J. G. Ganopolsky, I. Cornelissen, M. A. Suckow, M. J. Sandoval-Cooper, E. C. Brown, F. Noria, D. Gailani, Elliot Rosen, V. A. Ploplis, F. J. Castellino

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Activated protein C functions directly as an anticoagulant and indirectly as a profibrinolytic enzyme. To determine whether the fibrin deposition previously observed in PC-/- routine embryos and neonates was mediated through the FXI pathway, PC+/-/FXI-/- mice were generated and crossbred to produce double-deficient progeny (PC-/-/FXI-/-). PC-/-/FXI-/- mice survived the early lethality observed in the PC-/-/FXI+/+ neonates, with the oldest PC-/-/FXI-/- animal living to 3 months of age. However, the majority of these animals was sedentary and significantly growth-retarded. On sacrifice or natural death, all of these PC-/-/FXI-/- mice demonstrated massive systemic fibrin deposition with concomitant hemorrhage and fibrosis, as confirmed through histological analyses. Several of these animals also presented with enlarged lymph nodes and extensive lymphatic fluid in the thoracic cavity. Thus, although a number of the PC-/-/FXI-/- mice survived the lethal perinatal coagulopathy seen in the PC-/- neonates, they nonetheless succumbed to overwhelming thrombotic disease in later life. This combined deficiency state provided the first clear indication that the course of a severe thrombotic disorder could be manipulated by blocking the intrinsic pathway and provided the first opportunity to study a total protein C deficiency in an adult animal.

Original languageEnglish (US)
Pages (from-to)469-479
Number of pages11
JournalAmerican Journal of Pathology
Volume158
Issue number2
StatePublished - 2001
Externally publishedYes

Fingerprint

Factor XI
Protein C Deficiency
Fibrin
Thoracic Cavity
Protein C
Anticoagulants
Fibrosis
Embryonic Structures
Lymph Nodes
Hemorrhage
Enzymes
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Chan, J. C. Y., Ganopolsky, J. G., Cornelissen, I., Suckow, M. A., Sandoval-Cooper, M. J., Brown, E. C., ... Castellino, F. J. (2001). The characterization of mice with a targeted combined deficiency of protein C and factor XI. American Journal of Pathology, 158(2), 469-479.

The characterization of mice with a targeted combined deficiency of protein C and factor XI. / Chan, J. C Y; Ganopolsky, J. G.; Cornelissen, I.; Suckow, M. A.; Sandoval-Cooper, M. J.; Brown, E. C.; Noria, F.; Gailani, D.; Rosen, Elliot; Ploplis, V. A.; Castellino, F. J.

In: American Journal of Pathology, Vol. 158, No. 2, 2001, p. 469-479.

Research output: Contribution to journalArticle

Chan, JCY, Ganopolsky, JG, Cornelissen, I, Suckow, MA, Sandoval-Cooper, MJ, Brown, EC, Noria, F, Gailani, D, Rosen, E, Ploplis, VA & Castellino, FJ 2001, 'The characterization of mice with a targeted combined deficiency of protein C and factor XI', American Journal of Pathology, vol. 158, no. 2, pp. 469-479.
Chan JCY, Ganopolsky JG, Cornelissen I, Suckow MA, Sandoval-Cooper MJ, Brown EC et al. The characterization of mice with a targeted combined deficiency of protein C and factor XI. American Journal of Pathology. 2001;158(2):469-479.
Chan, J. C Y ; Ganopolsky, J. G. ; Cornelissen, I. ; Suckow, M. A. ; Sandoval-Cooper, M. J. ; Brown, E. C. ; Noria, F. ; Gailani, D. ; Rosen, Elliot ; Ploplis, V. A. ; Castellino, F. J. / The characterization of mice with a targeted combined deficiency of protein C and factor XI. In: American Journal of Pathology. 2001 ; Vol. 158, No. 2. pp. 469-479.
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