LOSS OF FIBRINOGEN RESCUES MICE FROM THE PLEIOTROPIC EFFECTS OF PLASMINOGEN DEFICIENCY

Plasmin(ogen) is an extracellular serine protease implicated in the ac tivation of latent growth factors and procollagenase, degradation of e xtracellular matrix components, and fibrin clearance. Plasminogen (Plg ) deficiency in mice results in high mortality, wasting, spontaneous g astrointestinal ulceration, rectal prolapse, and severe thrombosis. Fu rthermore, Plg-deficient mice display delayed wound healing following skin injury, a defect partly related to impaired keratinocyte migratio n. We generated mice deficient in Pig and fibrinogen (Fib) and show th at removal of fibrin(ogen) from the extracellular environment alleviat es the diverse spontaneous pathologies previously associated with Pig deficiency and corrects healing times. Mice deficient in Pig and Fib a re phenotypically indistinguishable from Fib-deficient mice. These dat a suggest that the fundamental and possibly only essential physiologic al role of Pig is fibronolysis.