A viable mouse model of factor X deficiency provides evidence for maternal transfer of factor X

摘要: Summary. Background: Activated factor X (FXa) is a vitamin K-dependent serine protease that plays pivotal role in blood coagulation by converting prothrombin to thrombin. There are no reports of humans with complete deficiency FX, and knockout murine F10 embryonic or perinatal lethal. Objective: We sought generate viable mouse model FX deficiency. Methods: We used socket-targeting construct F10-knockout mice eliminating exon 8 (knockout allele termed F10tm1Ccmt, abbreviated as ‘−’; wild-type ‘+’), plug-targeting expressing variant normal antigen levels but low activity [4–9% carrying the defect, Pro343Ser, Friuli (mutant F10tm2Ccmt, F)]. Results: F10 exhibited lethality. In contrast, homozygous [F10 (F/F)] had ∼5.5% (sufficient rescue both lethality), developed age-dependent iron deposition cardiac fibrosis. Interestingly, (−/F) 1–3% also showed Further study this provides evidence supporting maternal transfer survival. Conclusions: We demonstrate that, while absence incompatible survival, minimal sufficient lethal phenotype. This low-FX will facilitate development FX-directed therapies well investigation development.