Reduced Polymerization of Willebrand Factor in a Family of Pigs with a Variant of von Willebrand’s Disease

Sodium dodecyl sulfate electrophoresis on 2% agarose allows the separation of porcine Willebrand factor into multiple macromolecular complexes from 1.5 million to 21 million, molecular weight. In non-denaturing buffers these forms are resistant to alteration by 10^-4M mercaptoethanol, reduced glutathione, or cysteine. At sulfhydryl concentrations of 10^-4M both dithiothreitol (DTT) and dithioerythritol (DTE) seem to catalyze disulfide interchange evidence by the appearance of very high molecular weight polymers. Both DTT and DTE in the absence of detergent or other denaturants lowered the average complex size at sulfhydryl concentration of 10^-3M. Concomitant with the reduction in average polymer size there was a loss of ristocetin-Willebrand factor activity. A severe reduction of average molecular weight was found to be a characteristic of the Willebrand factor found in a genetically determined variant of the porcine model of von Willebrand’s disease. These observations provide a molecular basis for a qualitative version of the porcine disease in contrast to all previously described affected pigs which suffer a quantitative defieiency of Willebrand factor activity and antigen.