The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility.
The urokinase-type plasminogen activator receptor (uPAR) gene was disrupted 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 phenotypic abnormalities. There was no indication of loss of fetal animals based on the Mendelian pattern of transmission of the mutant uPAR gene. uPAR-/- mice carried no detectable uPAR in lung, spleen, and other tissues when measured both immunologically by Western blot analysis and functionally by ligand cross-linking analyses. In addition, activated peritoneal macrophages collected from uPAR-/- mice failed to promote plasminogen activation in vitro. The loss of the receptor also resulted 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 deficits, uPAR deficiency does not compromise fertility, development, or hemostasis. These mice provide a means to test the proposed function of uPA/uPAR in wound repair, atherogenesis, and tumor cell invasion in vivo.
Bugge
T H
TH
Division of Basic Science, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Suh
T T
TT
Flick
M J
MJ
Daugherty
C C
CC
Rømer
J
J
Solberg
H
H
Ellis
V
V
Danø
K
K
Degen
J L
JL
D000818:Animals; D001483:Base Sequence; D005314:Embryonic and Fetal Development; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D005298:Fertility; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D010958:Plasminogen / Q000378:metabolism; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014566:Urogenital System / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D004792:Enzyme Precursors; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator