| First Author | Eren M | Year | 2007 |
| Journal | J Thromb Haemost | Volume | 5 |
| Issue | 7 | Pages | 1500-8 |
| PubMed ID | 17439629 | Mgi Jnum | J:136979 |
| Mgi Id | MGI:3797454 | Doi | 10.1111/j.1538-7836.2007.02587.x |
| Citation | Eren M, et al. (2007) Reactive site-dependent phenotypic alterations in plasminogen activator inhibitor-1 transgenic mice. J Thromb Haemost 5(7):1500-8 |
| abstractText | BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of plasminogen activators (PAs) and plays a role in the regulation of a number of physiological processes including the degradation of extracellular matrix proteins, cell proliferation and migration, and intracellular signaling. AIM: To characterize the effects of durable expression of a stable form of human PAI-1 and to characterize important structure-function relationships in PAI-1 in vivo. METHODS: We developed transgenic mice lines overexpressing stable variants of human PAI-1 under the control of the murine preproendothelin-1 promoter and characterized the phenotypic alterations displayed by transgenic mice. RESULTS: Transgenic mice expressing an active form of human PAI-1 (PAI-1-stab) display complex phenotypic abnormalities including alopecia and hepatosplenomegaly. Reactive site mutant transgenic mice expressing inactive PAI-1 exhibit complete phenotypic rescue, while transgenic mice expressing PAI-1 with reduced affinity for vitronectin manifest all of the phenotypic abnormalities present in PAI-1-stab transgenic mice. CONCLUSIONS: The protease inhibitory activity of PAI-1 toward PAs and/or other serine proteases is necessary and sufficient to promote complex phenotypic abnormalities and mediates many of the physiological effects of PAI-1 in vivo. |
