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 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.
Dewerchin
M
M
Center for Transgene Technology and Gene Therapy, Vlaams Interuniversitair Institut voor Biotechnologie, Leuven, Belgium.
Nuffelen
A V
AV
Wallays
G
G
Bouché
A
A
Moons
L
L
Carmeliet
P
P
Mulligan
R C
RC
Collen
D
D
D000818:Animals; D001483:Base Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D018390:Gene Targeting; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000172:deficiency* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D011995:Recombination, Genetic; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator