A murine model of deep vein thrombosis: characterization and validation in transgenic mice.
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.
Cooley
Brian C
BC
Department of Orthopaedic Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA. bcooley@mcw.edu
Szema
Linda
L
Chen
Chao-Ying
CY
Schwab
Jeffrey P
JP
Schmeling
Gregory
G
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D002712:Chlorides; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004558:Electric Stimulation; D005165:Factor V / Q000235:genetics*; D005268:Femoral Vein / Q000187:drug effects / Q000473:pathology*; D005290:Ferric Compounds; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017354:Point Mutation; D015203:Reproducibility of Results; D020246:Venous Thrombosis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D000925:Anticoagulants; D002712:Chlorides; D005290:Ferric Compounds; C095381:factor V Leiden; D005165:Factor V; D006493:Heparin; C024555:ferric chloride