Hamostaseologie 2009; 29(01): 17-20
DOI: 10.1055/s-0037-1616933
Original article
Schattauer GmbH

Mouse models to study von Willebrand factor structure-function relationships in vivo

C. V. Denis
1   INSERM U 770; Université Paris-Sud, France
,
I. Marx
1   INSERM U 770; Université Paris-Sud, France
,
I. Badirou
1   INSERM U 770; Université Paris-Sud, France
,
R. Pendu
1   INSERM U 770; Université Paris-Sud, France
,
O. Christophe
1   INSERM U 770; Université Paris-Sud, France
› Author Affiliations
Further Information

Publication History

Publication Date:
29 December 2017 (online)

Summary

Von Willebrand factor (VWF) structure-function relationship has been studied only through in vitro approaches. The VWF-deficient mouse model has been extremely useful to examine the in vivo function of VWF but does not allow a more subtle analysis of the relative importance of its different domains. However, considering the large size of VWF and its capacity to interact with various ligands in order to support platelet adhesion and aggregation, the necessity to evaluate independently these interactions appeared increasingly crucial. A recently developed technique, known as hydrodynamic injection, which allows transient expression of a transgene by mouse hepatocytes, proved very useful in this regard. Indeed, transient expression of various VWF mutants in VWF-deficient mice contributed to improve our knowledge about the role of VWF interaction with subendothelial collagens and with platelets receptors in VWF roles in haemostasis and thrombosis. These findings can provide new leads in the development of anti-thrombotic therapies.

 
  • References

  • 1 De Meyer SF, Vandeputte N, Pareyn I. et al. Restoration of plasma von Willebrand factor deficiency is sufficient to correct thrombus formation after gene therapy for severe von Willebrand disease. Arterioscler Thromb Vasc Biol 2008; 28: 1621-1626.
  • 2 Feng DM, He CX, Miao CY. et al. Conditions affecting hydrodynamics-based gene delivery into mouse liver in vivo. Clin Exp Pharmacol Physiol 2004; 31: 850-855.
  • 3 Lankhof H, Wu YP, Vink T. et al. Role of the glycoprotein Ib-binding A1 repeat and the RGD sequence in platelet adhesion to human recombinant von Willebrand factor. Blood 1995; 86: 1035-1042.
  • 4 Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther 1999; 6: 1258-1266.
  • 5 Marx I, Lenting PJ, Adler T. et al. Correction of bleeding symptoms in von Willebrand factor-deficient mice by liver-expressed von Willebrand factor mutants. Arterioscler Thromb Vasc Biol 2008; 28: 419-424.
  • 6 Marx I, Christophe OD, Lenting PJ. et al. Altered thrombus formation in von Willebrand factordeficient mice expressing von Willebrand factor variants with defective binding to collagen or GPIIbIIIa. Blood 2008; 112: 603-609.
  • 7 Matsushita T, Meyer D, Sadler JE. Localization of von willebrand factor-binding sites for platelet glycoprotein Ib and botrocetin by charged-to-alanine scanning mutagenesis. J Biol Chem 2000; 275: 11044-11049.
  • 8 Ribba AS, Loisel I, Lavergne JM. et al. Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen. Thromb Haemost 2001; 86: 848-854.
  • 9 Romijn RA, Westein E, Bouma B. et al. Mapping the collagen-binding site in the von Willebrand factor-A3 domain. J Biol Chem 2003; 278: 15035-15039.
  • 10 Ruggeri ZM. Von Willebrand factor: Looking back and looking forward. Thromb Haemost 2007; 98: 55-62.
  • 11 Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update. Semin Hematol 2005; 42: 15-28.
  • 12 Wagner DD. Cell biology of von Willebrand factor. Ann Rev Cell Biol 1990; 6: 217-246.