A knockout for knockin.

摘要

By introducing an engineered anticoagulant-selective prothrombin mutant within the endogenous prothrombin gene (F2), Flick and colleagues generated a multifaceted phenotype that opens doors for new dimensions in genetically modified mouse research. Endogenous expression of engineered WE-thrombin (W215A/E217A), which conveys only the anticoagulant activity profile of thrombin but not its procoagulant activity profile, permits investigators to "peel the layers of the onion" of thrombin's multi-substrate specificity while learning important lessons about thrombin's diverse activities in normal physiology and pathophysiology. This innovative approach presents numerous unique opportunities, but also identifies new challenges and highlights the need to refurbish our current view on structure-function of coagulation proteases.