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. 1996 Feb 1;97(3):870–878. doi: 10.1172/JCI118489

Generation and characterization of urokinase receptor-deficient mice.

M Dewerchin 1, A V Nuffelen 1, G Wallays 1, A Bouché 1, L Moons 1, P Carmeliet 1, R C Mulligan 1, D Collen 1
PMCID: PMC507128  PMID: 8609247

Abstract

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.

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Selected References

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