Effects of Disruption of The Plasminogen Gene on Thrombosis, Growth, and Health in Mice

Abstract

Plasminogen-deficient mice survive embryonic development but develop spontaneous fibrin deposition due to impaired thrombolysis and suffer retarded growth and reduced fertility and survival. The Plg-/- phenotype is reminiscent of the combined tPA-/-:uPA-/- phenotype, which suggests that there is no significant additional pathway for physiological plasminogen activation in mice.

Generation and characterization of urokinase receptor-deficient mice.

“…Absence of functional receptor in u-PAR Ϫ/Ϫ mice was demonstrated by the lack of specific binding of an aminoterminal fragment of murine u-PA (containing amino acid res- u-PAR-deficiency did not compromise embryonic development and viability of the mice, in accordance with previous observations on mice deficient for other components of the fibrinolytic system including u-PA and/or t-PA (16), plasminogen (34), and the inhibitors plasminogen activator inhibitor type-1 (23) or ␣ 2 -macroglobulin (35), and implying a less essential role for the plasminogen activation system and u-PA/u-PAR in embryo implantation, development, and viability than previously assumed (36). u-PAR Ϫ/Ϫ mice displayed normal growth and fertility, and no histological abnormalities were found in tissues from 4.5-wk-old mice.…”

Plasminogen activator/plasmin system in arthritis and inflammation: Friend or foe?

“…The recent availability of gene-deficient mice (for example, deficient in plasminogen, uPA, and tPA) has helped to clarify the roles of these components in the steady state and in pathology. For example, Plg Ϫ/Ϫ mice are severely impaired in their ability to clear fibrin deposits (4,5). This phenotype is similar to that noted for the combined uPA Ϫ/Ϫ ;tPA Ϫ/Ϫ phenotype and is more severe than that for either PA-deficient mouse alone, suggesting that there is no significant additional pathway for physiologic plasminogen activation in mice (5) (but see below).…”

Therapy with a Purified Plasminogen Concentrate in an Infant with Ligneous Conjunctivitis and Homozygous Plasminogen Deficiency

“…19,20,32 Tracheobronchial fibrin deposition has been observed in our patient, in others with ligneous conjunctivitis, 2,5,13,33 and in plasminogen-deficient mice. 34 The fibrin deposits impair the ciliary system of the tracheobronchial tree and support bacterial growth, predisposing the patient to multiple sinobronchial infections. The ear involvement in our patient and others 8 is attributable to fibrin deposition in the middle ear.…”