In vertebrates, formation of a clot at a site of blood vessel injury requires a group
of plasma proteins (coagulation factors) that regulate generation of the protease α-
thrombin. α-Thrombin mediates a number of key activities during clot formation, including
conversion of soluble plasma fibrinogen into an insoluble fibrin mesh, activation of
platelets, and stimulation of vascular endothelial cells. While α-thrombin is required for
life, dysregulated generation of this protease can contribute to life-threatening thrombotic
disorders and consumptive coagulopathies. The coagulation factors were originally
identified and characterized using plasma clotting assays. While deficiency of any single
coagulation factor results in an abnormal result in one or more of these in vitro assays, the
severity of the associated bleeding disorder can range from fatal hemorrhage to complete
absence of symptoms. Genes for coagulation factors have been manipulated by a variety of
“knockout”, “knock-in”, and transgenic strategies in mice. In this chapter, we review
insights gained into hemostasis, thrombosis and wound healing through studies involving
mouse models of coagulation deficiencies. The chapter is divided into sections focusing on
deficiencies associated with lethal phenotypes (prothrombin, tissue factor, tissue factor
pathway inhibitor, factor V, factor VII, factor X and γ-glutamyl carboxylase), deficiencies
associated with severe bleeding disorders that do not compromise viability (fibrinogen,
factor VIII, factor IX and factor XIII), and those not associated with abnormal hemostasis
(factor XI, factor XII and high molecular weight kininogen) and the translational value of
each model in drug discovery and development is discussed.
Keywords: Animal model, coagulation deficiency, coagulation factor, drug
discovery, drug development, hemostasis, mouse, prothrombin, thrombosis, tissue
factor, translational model.
