Disruption of the kringle 1 domain of prothrombin leads to late onset mortality in zebrafish.

ABSTRACT: The ability to prevent blood loss in response to injury is a conserved function of all vertebrates. Complete deficiency of the central clotting enzyme prothrombin has never been observed in humans and is incompatible with postnatal life in mice, thus limiting the ability to study its role in vivo. Zebrafish are able to tolerate severe hemostatic deficiencies that are lethal in mammals. We have generated a targeted genetic deletion in the kringle 1 domain of zebrafish prothrombin. Homozygous mutant embryos develop normally into the mid-juvenile stage but demonstrate complete mortality by 2 months of age primarily due to internal hemorrhage. Mutants are unable to form occlusive venous and arterial thrombi in response to endothelial injury, a defect that was phenocopied using direct oral anti

SUBMITTER: Grzegorski SJ 

PROVIDER: S-EPMC7055286 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature