Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life

Mariko Nagashima, Zheng Feng Yin, Lei Zhao, Kathy White, Yanhong Zhu, Nina Lasky, Meredith Halks-Miller, George J. Broze, William P. Fay, John Morser

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

To investigate the consequence of deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI), we generated homozygous TAFI-deficient mice by targeted gene disruption. Intercrossing of heterozygous TAFI mice produced offspring in the expected Mendelian ratio, indicating that transmission of the mutant TAFI allele did not lead to embryonic lethality. TAFI-deficient mice developed normally, reached adulthood, and were fertile. No gross physical abnormalities were observed up to 24 months of age. Hematological analysis of TAFI-deficient mice did not show any major differences including plasma fibrinogen level, prothrombin time, and activated partial thromboplastin time. TAFI-deficient mice did not suffer from excess bleeding as determined by blood loss following tail transection, although their plasma failed to prolong clot lysis time in vitro. In vivo, TAFI deficiency did not influence occlusion time in either an arterial or a venous injury model. TAFI deficiency did not improve survival rate compared with the wild-type in thrombin-induced thromboembolism, factor X coagulant protein-induced thrombosis, and endotoxin-induced disseminated intravascular coagulation. Furthermore, TAFI deficiency did not alter kaolin-induced writhing response, implying that TAFI does not play a major role in bradykinin catabolism. The current study demonstrates that TAFI deficiency does not change normal responses to acute challenges.

Original languageEnglish
Pages (from-to)101-110
Number of pages10
JournalJournal of Clinical Investigation
Volume109
Issue number1
DOIs
StatePublished - Jan 1 2002

Fingerprint Dive into the research topics of 'Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life'. Together they form a unique fingerprint.

  • Cite this

    Nagashima, M., Yin, Z. F., Zhao, L., White, K., Zhu, Y., Lasky, N., Halks-Miller, M., Broze, G. J., Fay, W. P., & Morser, J. (2002). Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. Journal of Clinical Investigation, 109(1), 101-110. https://doi.org/10.1172/JCI0212119