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A murine model of deep vein thrombosis: characterization and validation in transgenic mice. Thromb Haemost 2005 Sep;94(3):498-503

Date

11/05/2005

Pubmed ID

16268462

DOI

10.1160/TH05-03-0170

Scopus ID

2-s2.0-24944434705 (requires institutional sign-in at Scopus site)   38 Citations

Abstract

Deep vein thrombosis (DVT) occurs with high prevalence in association with a number of risk factors, including major surgery, trauma, obesity, bed rest (> 5 days), cancer, a previous history of DVT, and several predisposing prothrombotic mutations. A novel murine model of DVT was developed for applications to preclinical studies of transgenically constructed prothrombotic lines and evaluation of new antithrombotic therapies.A transient direct-current electrical injury was induced in the common femoral vein of adult C57BI/6 mice. A non-occlusive thrombus grew, peaking in size at 30 min, and regressing by 60 min, as revealed by histomorphometric volume reconstruction of the clot. Pre-heparinization greatly reduced clot formation at 10, 30, and 60 min (p < 0.01 versus non-heparinized). Homozygous FactorV Leiden mice (analogous to the clinical FactorV Leiden prothrombotic mutation) on a C57Bl/6 background had clot volumes more than twice those of wild-types at 30 min (0.121 +/- 0.018 mm3 vs. 0.052 +/- 0.008 mm3, respectively; p < 0.01). Scanning electron microscopy revealed a clot surface dominated by fibrin strands, in contrast to arterial thrombi which showed a platelet-dominated structure. This new model of DVT presents a quantifiable approach for evaluating thrombosis-related murine transgenic lines and for comparatively evaluating new pharmacologic approaches for prevention of DVT.

Author List

Cooley BC, Szema L, Chen CY, Schwab JP, Schmeling G

Author

Jeffrey P. Schwab MD Adjunct Professor in the Orthopaedic Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Anticoagulants
Chlorides
Coronary Artery Disease
Coronary Vessels
Disease Models, Animal
Drug Evaluation, Preclinical
Electric Stimulation
Factor V
Femoral Vein
Ferric Compounds
Heparin
Mice
Mice, Inbred C57BL
Mice, Transgenic
Point Mutation
Reproducibility of Results
Venous Thrombosis