THE RECEPTOR FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IS NOT ESSENTIAL FOR MOUSE DEVELOPMENT OR FERTILITY

The urokinase-type plasminogen activator receptor (uPAR) gene was disr upted in mice in order to explore the role of cell surface-associated plasminogen activation in development and hemostasis. Homozygous, uPAR (-/-) mice were born and survived to adulthood with no overt phenotypi c abnormalities. There was no indication of loss of fetal animals base d on the Mendelian pattern of transmission of the mutant uPAR gene. uP AR(-/-) mice carried no detectable uPAR in lung, spleen, and other tis sues when measured both immunologically by Western blot analysis and f unctionally by ligand cross-linking analyses. In addition, activated p eritoneal macrophages collected from uPAR(-/-) mice failed to promote plasminogen activation in vitro. The loss of the receptor also resulte d in a redistribution of uPA in some tissues but had no impact on pro- uPA activation in the urogenital tract. Thus, in the absence of other challenging factors such as infection, injury, or other functional def icits, uPAR deficiency does not compromise fertility, development, or hemostasis. These mice provide a means to test the proposed function o f uPA/uPAR in wound repair, atherogenesis, and tumor cell invasion in vivo.