Acute and severe coagulopathy in adult mice following silencing of hepatic antithrombin and protein C production

摘要: Mice deficient in the anticoagulants antithrombin (Serpinc1) or protein C (Proc) display premature death due to thrombosis-related coagulopathy, thereby precluding their use gene function studies and thrombosis models. We used RNA interference silence Serpinc1 and/or Proc normal adult mice. The severe coagulopathy that followed combined "knockdown" of these genes is reported. Two days after siRNA injection, thrombi (occlusive) were observed vessels (large medium-sized) multiple tissues, hemorrhages prominent ocular, mandibular, maxillary areas. Tissue fibrin deposition reduction plasma fibrinogen accompanied this phenotype. was prevented by dabigatran etexilate treatment. Silencing alone yielded a comparable but milder phenotype with later onset. absent when targeted alone. conclude allows for evaluation vivo provides novel, controlled mouse model spontaneous venous thrombosis.