Generation and characterization of urokinase receptor-deficient mice

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...

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Bibliographic Details
Published in:	The Journal of clinical investigation Vol. 97; no. 3; pp. 870 - 878
Main Authors:	Dewerchin, M, Nuffelen, A V, Wallays, G, Bouché, A, Moons, L, Carmeliet, P, Mulligan, R C, Collen, D
Format:	Journal Article
Language:	English
Published:	United States 01-02-1996
Subjects:	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
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0021-9738
DOI:	10.1172/jci118489