Generation and characterization of urokinase receptor-deficient mice

J Clin Invest. 1996 Feb 1;97(3):870-8. doi: 10.1172/JCI118489.


Mice homozygously deficient for the urokinase-type plasminogen activator (u-PA) receptor (u-PAR-1-) were generated by homologous recombination in D3, embryonic stem cells. The genomic sequences comprising exon 2 through 5 of the u-PAR gene were replaced by the neomycin resistance gene, resulting in inactivation of both u-PAR splice variants. The inactivated u-PAR allele was transmitted via mendelian inheritance, and fertility. Inactivation of u-PAR was confirmed by the absence of binding of rabbit anti-murine u-PAR or of an aminoterminal fragment of murine u-PA (mu-PA.1-48) to u-PAR-1- embryonic fibroblasts and macrophages. u-PAR-1- mice displayed normal lysis of a murine plasma clot injected via the jugular vein. Invasion of macrophages into the peritoneal cavity after thioglycollate stimulation was similar in u-PAR-1- and u-PAR-1- mice. u-PAR-1- peritoneal macrophages had a threefold decreased initial rate of u-PA-mediated plasminogen activation in vitro but degraded extracellular matrix proteins in vitro as efficiently as u-PAR-1- macrophages.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Enzyme-Linked Immunosorbent Assay
  • Fibrinolysin / metabolism
  • Fibrinolysis / physiology*
  • Gene Targeting
  • Macrophages, Peritoneal / physiology
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Plasminogen Activators / deficiency*
  • Plasminogen Activators / genetics
  • Polymerase Chain Reaction
  • Receptors, Cell Surface / deficiency*
  • Receptors, Cell Surface / genetics
  • Receptors, Urokinase Plasminogen Activator
  • Recombination, Genetic
  • Urokinase-Type Plasminogen Activator / metabolism*


  • Plaur protein, mouse
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Plasminogen Activators
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator