The plasminogen activator inhibitor-2 gene is not required for normal murine development or survival.
Plasminogen activator inhibitor-2 (PAI-2), a member of the serpin gene family, is thought to serve as a primary regulator of plasminogen activation in the extravascular compartment. High levels of PAI-2 are found in keratinocytes, monocytes, and the human trophoblast, the latter suggesting a role in placental maintenance or embryo development. The primarily intracellular distribution of PAI-2 also may indicate a unique regulatory role in a protease-dependent cellular process such as apoptosis. To examine the potential functions of PAI-2 in vivo, we generated PAI-2-deficient mice by gene targeting in embryonic stem cells. Homozygous PAI-2-deficient mice exhibited normal development, survival, and fertility and were also indistinguishable from normal controls in response to a bacterial infectious challenge or endotoxin infusion. No differences in monocyte recruitment into the peritoneum were observed after thioglycollate injection. Epidermal wound healing was equivalent among PAI-2 -/- null and control mice. Finally, crossing PAI-2 -/- with PAI-1 -/- mice to generate animals deficient in both plasminogen activator inhibitors failed to uncover an overlap in function between these two related proteins.
Dougherty
K M
KM
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA.
Pearson
J M
JM
Yang
A Y
AY
Westrick
R J
RJ
Baker
M S
MS
Ginsburg
D
D
D000818:Animals; D015139:Blotting, Southern; D018390:Gene Targeting / Q000379:methods; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2