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A murine model of deep vein thrombosis Characterization and validation in transgenic mice

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH05-03-0170
Issue: 2005: 94/3 (Sep) pp. 469-691
Pages: 498-503

A murine model of deep vein thrombosis Characterization and validation in transgenic mice

Brian C. Cooley, Linda Szema, Chao-Ying Chen, Jeffrey P. Schwab, Gregory Schmeling
Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Summary

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 C57Bl/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