Loss of factor VIII in zebrafish rebalances antithrombin deficiency but has a limited bleeding diathesis.

ABSTRACT: Deficiencies in coagulation factor VIII (FVIII, F8) result in the bleeding disorder hemophilia A. An emerging novel therapeutic strategy for bleeding disorders is to enhance hemostasis by limiting natural anticoagulants, such as antithrombin (AT3). To study pro/anticoagulant hemostatic balance in an in vivo model, we used genome editing to create null alleles for f8 and von Willebrand factor (vwf) in zebrafish, a model organism with a high degree of homology to the mammalian hemostatic system and unique attributes, including external development and optical transparency. f8 homozygous mutant larvae surprisingly formed normal thrombi when subjected to laser-mediated endothelial injury, had no overt signs of hemorrhage, but had a modest increase in mortalit

SUBMITTER: Richter CE 

PROVIDER: S-EPMC11785011 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature