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Updated: Jul 15, 2026
Transient Expression of Proteins by Hydrodynamic Gene Delivery in Mice
Published on: May 5, 2014
Reactive site-dependent phenotypic alterations in plasminogen activator inhibitor-1 transgenic mice
M Eren1, L A Gleaves, J B Atkinson
1Division of Cardiovascular Medicine, Department of Medicine and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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.
