Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

الملخص EN

von Willebrand disease (VWD) is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF).

VWF is a secreted glycoprotein that circulates as large multimers.

While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis.

The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals.

The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis.

Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated.

In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure.

Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs) in cell culture.

Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium.

These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.