A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state

Journal of Clinical Investigation

Volumn 101, Issue 9, 1998, Pages 1983-1991

  Weiler Guettler, Hartmut ^a,b   Christie, Patricia D ^a   Beeler, David L ^a   Healy, Aileen M ^c   Hancock, Wayne W ^d   Rayburn, Helen ^a   Edelberg, Jay M ^a   Rosenberg, Robert D ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b BLOOD RESEARCH INSTITUTE   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Animal model; Development; Gene targeting; Protein C; Thrombosis

Indexed keywords

PROTEIN C; THROMBIN; THROMBOMODULIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BLOOD CLOTTING; GENE TARGETING; LETHALITY; MOUSE; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; THROMBOSIS;

EID: 0032080409     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI2006     Document Type: Article

References (43)

1. Esmon, C.T., and W.G. Owen. 1981. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc. Natl. Acad. Sci. USA. 78:2249-2252.
2. Esmon, N.L., R.C. Carroll, and C.T. Esmon. 1983. Thrombomodulin blocks the ability of thrombin to activate platelets. J. Biol. Chem. 258:12238-12242.
3. Esmon, C.T., N.L. Esmon, and K.W. Harris. 1982. Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. J. Biol. Chem. 257:7944-7947.
4. Dahlback, B. 1995. The protein C anticoagulant system: inherited defects as basis for venous thrombosis. Thromb. Res. 77:1-43.
5. Bertina, R.M., B.P. Koeleman, T. Koster, F.R. Rosendaal, R.J. Dirven, H. van de Ronde, and P.H. Reitsma. 1994. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 369:64-67.
6. Ohlin, A.K., and R.A. Marlar. 1995. The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease. Blood. 85:330-336.
7. van der Velden, P.A., T. Krommenhoek-Van Es, C.F. Allaart, R.M. Bertina, and P.H. Reitsma. 1991. A frequent thrombomodulin amino acid dimorphism is not associated with thrombophilia. Thromb. Haemost. 65:511-513.
8. Faioni, E.M., G. Merati, F. Peyvandi, P.M. Bettini, and P.M. Mannucci. 1997. The G(1456) to T mutation in the thrombomodulin gene is not frequent in patients with venous thrombosis. Blood. 89:1467.
9. Norlund, L., J. Holm, B. Zoller, and A.K. Ohlin. 1997. A common thrombomodulin amino acid dimorphism is associated with myocardial infarction. Thromb. Haemost. 77:248-251.
10. Healy, A.M., H.B. Rayburn, R.D. Rosenberg, and H. Weiler. 1995. Absence of the blood-clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Proc. Natl. Acad. Sci. USA. 92:850-854.
11. Weiler-Guettler, H., W.C. Aird, H. Rayburn, M. Husain, and R.D. Rosenberg. 1996. Developmentally regulated gene expression of thrombomodulin in postimplantation mouse embryos. Development. 122:2271-2281.
12. Weiler-Guettler, H., W.C. Aird, M. Husain, H. Rayburn, and R.D. Rosenberg. 1996. Targeting of transgene expression to the vascular endothelium of mice by homologous recombination at the thrombomodulin locus. Circ. Res. 78:180-187.
13. Carmeliet, P., L. Schoonjans, L. Kieckens, B. Ream, J. Degen, R. De Vos, J.J. van den Oord, D. Collen, and R.C. Mulligan. 1994. Physiological consequences of loss of plasminogen activator gene function in mice. Nature. 368: 419-424.
14. Esmon, N.L., W.G. Owen, and C.T. Esmon. 1982. Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J. Biol. Chem. 257:859-864.
15. Kennel, S.J., T. Lankford, B. Hughes, and J.A. Hotchkiss. 1988. Quantitation of a murine lung endothelial cell protein, P112, with a double monoclonal antibody assay. Lab. Invest. 59:692-701.
16. Swank, R.T., and K.D. Munkres. 1971. Molecular weight analysis of oligopeptides by electrophoresis in polyacrylamide gel with sodium dodecyl sulfate. Anal. Biochem. 39:462-477.
17. Dixon, M., and E.C. Webb. 1979. Enzymes. Academic Press, New York. 381-389.
18. Lodge, P.A., C.E. Haisch, and F.T. Thomas. 1992. A simple method of vascular endothelial cell isolation. Transplant. Proc. 24:2816-2817.
19. Orthner, C.L., B. Kolen, and W.N. Drohan. 1993. A sensitive and facile assay for the measurement of activated protein C activity levels in vivo. Thromb. Haemost. 69:441-447.
20. Kaufman, M.H. 1992. The Atlas of Mouse Development. Academic Press, San Diego, CA.
21. Hui, K.Y., E. Haber, and G.R. Matsueda. 1983. Monoclonal antibodies to a synthetic fibrin-like peptide bind to human fibrin but not fibrinogen. Science. 222:1129-1132.
22. Dvorak, H.F., D.M. Form, E.J. Manseau, and B.D. Smith. 1984. Pathogenesis of desmoplasia. J. Natl. Cancer Inst. 73:1195-1201.
23. Ford, V.A., J.E. Wilkinson, and S.J. Kennel. 1993. Thrombomodulin distribution during murine development. Roux's Arch. Dev. Biol. 202:364-370.
24. Strickland, S., and W.G. Richards. 1992. Invasion of the trophoblasts. Cell. 71:355-357.
25. Cross, J.C., Z. Werb, and S.J. Fisher. 1994. Implantation and the placenta: key pieces of the development puzzle. Science. 266:1508-1518.
26. Sappino, A.P., J. Huarte, D. Belin, and J.D. Vassalli. 1989. Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos. J. Cell Biol. 109:2471-2479.
27. Clarke, J.H., D.R. Light, E. Blasko, J.F. Parkinson, M. Nagashima, K. McLean, W.H. Andrews, J. Morser, and C.B. Glaser. 1993. The short loop between epidermal growth factor-like domains 4 and 5 is critical for human thrombomodulin function. J. Biol. Chem. 268:6309-6315.
28. Conard, J., K.A. Bauer, A. Gruber, J.H. Griffin, H.P. Schwarz, M. Horellou, and R.D. Rosenberg. 1993. Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. Blood. 82:1159-1164.
29. Lawson, C.A., S.D. Yan, S.F. Yan, H. Liao, Y.S. Zhou, J. Sobel, W. Kisiel, D.M. Stern, and D.J. Pinsky. 1997. Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation. J. Clin. Invest. 99:1729-1738.
30. Stearns-Kurosawa, D.J., S. Kurosawa, J.S. Mollica, G.L. Ferrell, and C.T. Esmon. 1996. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc. Natl. Acad. Sci. USA. 93:10212-10216.
31. Zhang, Y., H. Weiler-Guettler, J. Chen, O. Wilhelm, Y. Deng, F. Qui, K. Nakagawa, M. Klevesath, S. Wilhelm, H. Bohrer, et al. 1998. Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity. J. Clin. Invest. 101:1301-1309.
32. Carmeliet, P., N. Mackman, L. Moons, T. Luther, P. Gressens, H. Demunck, M. Kasper, G. Breier, P. Evrard, M. Muller, et al. 1996. Role of tissue factor in embryonic blood vessel development. Nature. 383:73-75.
33. Toomey, J.R., K.E. Kratzer, N.M. Lasky, J.J. Stanton, and G.J. Broze, Jr. 1996. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood. 88:1583-1587.
34. Bugge, T.H., O. Xiao, K.W. Kombrinck, M.J. Flick, K. Holmback, M.J. Danton, D.P. Witte, K. Fujikawa, E.W. Davie, and J.L. Degen. 1996. Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc. Natl. Acad. Sci. USA. 93:6258-6263.
35. Cui, J., K.S. O'Shea, A. Purkayastha, T.L. Saunders, and D. Ginsburg. 1996. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature. 384:66-68.
36. Suh, T.T., K. Holmback, N.J. Jensen, C.C. Daugherty, K. Small, D.I. Simon, S. Potter, and J.L. Degen. 1995. Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. Genes Dev. 9: 2020-2033.
37. Bugge, T.H., K.W. Kombrinck, M.J. Flick, C.C. Daugherty, and M. Danton. 1996. Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency. Cell. 87:709-719.
38. Ford, V.A., C. Stringer, and S.J. Kennel. 1992. Thrombomodulin is preferentially expressed in Balb/c lung microvessels. J. Biol. Chem. 267:5446-5450.
39. Dittman, W.A., and P.W. Majerus. 1990. Structure and function of thrombomodulin: a natural anticoagulant. Blood. 75:329-336.
40. Meade, T.W., G.J. Miller, and R.D. Rosenberg. 1992. Characteristics associated with the risk of arterial thrombosis and the prethrombotic state. In Thrombosis in Cardiovascular Disorders. V. Fuster and M. Verstraete, editors. W.B. Saunders Company, Philadelphia. 79-97.
41. Zoeller, B., A. Hillarp, E. Berntorp, and B. Dahlhack. 1997. Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis. Ann. Rev. Med. 48:45-58.
42. Miletich, J.P., S.M. Prescott, R. White, P.W. Majerus, and E.G. Bovill. 1993. Inherited predisposition to thrombosis. Cell. 72:477-480.
43. Lane, D.A., P.M. Mannucci, K.A. Bauer, R.M. Bertina, N.P. Bochkov, V. Boulyjenkov, B. Dahlback, E.K. Ginter, J.P. Miletich, F.R. Rosendaal, et al. 1996. Inherited thrombophilia: Part 1. Thromb. Haemost. 76:651-662.