| First Author | Raife TJ | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 11 | Pages | 2509-17 |
| PubMed ID | 21885846 | Mgi Jnum | J:191461 |
| Mgi Id | MGI:5461785 | Doi | 10.1161/ATVBAHA.111.236828 |
| Citation | Raife TJ, et al. (2011) Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis. Arterioscler Thromb Vasc Biol 31(11):2509-17 |
| abstractText | OBJECTIVE: We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. METHODS AND RESULTS: Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (P<0.01) and lung (P<0.001). Activation of endogenous protein C following infusion of thrombin was decreased by 90% in knock-in mice compared with wild-type mice (P<0.05). Carotid artery thrombosis induced by photochemical injury occurred more rapidly in knock-in mice (12+/-3 minutes) than in wild-type mice (31+/-6 minutes; P<0.05). No differences in serum cytokine levels were detected between knock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. CONCLUSION: Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo. |
