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

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.
Authors	Mariko Nagashima, Zheng-Feng Yin, Lei Zhao, Kathy White, Yanhong Zhu, Nina Lasky, Meredith Halks-Miller, George J Broze Jr, William P Fay, John Morser
Journal	The Journal of clinical investigation (J Clin Invest) Vol. 109 Issue 1 Pg. 101-10 (Jan 2002) ISSN: 0021-9738 [Print] United States
PMID	11781355 (Publication Type: Journal Article)
Chemical References	Carboxypeptidase B2
Topics	Animals Carboxypeptidase B2 (deficiency, genetics, physiology) Disease Models, Animal Disseminated Intravascular Coagulation (blood, etiology) Female Fertility Fibrinolysis Gene Targeting Homozygote In Vitro Techniques Male Mice Mice, Inbred C57BL Mice, Knockout Phenotype Thrombosis (blood, etiology)

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