Dataset Information

Use of a mouse model to elucidate the phenotypic effects of the von Willebrand factor cleavage mutants, Y1605A/M1606A and R1597W.

ABSTRACT:

Background

von Willebrand Factor (VWF) is tightly regulated by the metalloproteinase ADAMTS13, which cleaves VWF to reduce VWF multimer size and binding affinity for collagen and platelets.

Objective

This study examines two VWF mutations, R1597W (enhanced cleavage) and Y1605A-M1606A (decreased cleavage), to determine their impact on VWF, in addition to ADAMTS13-mediated cleavage.

Methods

In vitro mouse ADAMTS13 digestions were performed on recombinant proteins. VWF knockout mice received hydrodynamic injections of mouse Vwf cDNA, following which VWF antigen, multimer profile and VWF propeptide levels were determined. A ferric chloride injury model of thrombosis was also evaluated.