Loss of protein C vs protein S results in discrepant thrombotic phenotypes.

ABSTRACT:

Abstract

Venous thrombosis is a leading cause of morbidity/mortality and associated with deficiencies of the anticoagulant protein C (PC; PROC) and its cofactor, protein S (PS; PROS1). Heterozygous mutations increase the risk of adult-onset thrombosis, whereas homozygous mutations result in pre/neonatal lethal thrombosis. Phenotypes of patients with PC and PS deficiency are generally considered clinically indistinguishable. Here, we generate proc (zebrafish PROC ortholog) and pros1 knockouts through genome editing in zebrafish and uncover partially discordant phenotypes. proc-/- mutants exhibited ∼70% lethality at 1 year of age, whereas pros1-/- survival was unaffected. Induced venous endothelial injury in both mutants revealed reduced occlusive thrombus formation. This is consiste

SUBMITTER: Ku CJ 

PROVIDER: S-EPMC11821410 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature