Genetic models of hemostasis and thrombosis

Given that knock-outs of prothrombotic factors yield mice with bleeding tendencies, it follows that deletion of factors in the fibrinolytic pathway results in increased thrombotic susceptibility in mice. Plasminogen (Bugge et al. 1995 Ploplis et al. 1995), tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and the combined t-PA/u-PA knock-out (Carmeliet et al. 1994) result in mice that 

Sarkar R, Naas T et aL (1996) Further characterization of Factor VUI-deficient mice created by gene targeting RNA and protein studies. Blood 88 3446-3450 Bugge TH, Suh TT, Flick MJ et al. (1995) The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility. J Bio Chem 270 16886-16894 

Bugge TH, Xiao Q, Kombrinck KW et al. (1996) Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc Natl Acad Sci USA 93 6258-6263 

Carmeliet P, Cohen D (1999) New developments in the molecular biology of coagulation and fibrinolysis. In Handbook of Experimental Pharmacology. Vol. 132, Antithrombotics. Springer Verlag, Berlin, pp 41-76 Carmeliet P, Mackman N, Moons L et al. (1996) Role of tissue factor in embryonic blood vessel development. Nature 383 73-75 

Carmeliet P, Schoonjans L, Kieckens L et al. (1994) Physiological consequences of loss of plasminogen activator gene function in mice. Nature 368 419-424 Carmeliet P, Stassen JM, Schoonjans L et al. (1993) Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, thrombolysis. J Clin Invest 92 2756-2760 

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