Gene targeting and gene transfer studies of the biological role of the plasminogen/plasmin system.

A possible role of the plasminogen/plasmin or fibrinolytic system in several biological processes has been implied from correlations between fibrinolytic activity and (patho)physiological phenomena. However, such indirect evidence does not allow to definitively establish the biological relevance of this system. Two recently developed technologies, gene targeting and gene transfer, have allowed to more definitively characterize the in vivo role of gene products. The consequences of gain or loss of function of fibrinolytic system components on reproduction, development, health, survival and on hemostasis, thrombosis, neointima formation, tissue remodeling, brain function, malignancy and neovascularization is summarized below. In addition, the possible use of transgenic mice to study gene regulation or to generate monoclonal antibodies against conserved epitopes in the targeted proteins is discussed.