Impact of administration of murine VWF cDNA plasmid on bleeding time of VWF^–/– mice. Mice were assessed for the time required for bleeding to stop after a transected tail vein wound. After 10 minutes, bleeding was stopped by cauterization. Each data point represents a single animal. Wild-type mice stopped bleeding 2 to 3 minutes after wounding. Forty-eight hours after administration with saline, naive VWF^–/– mice and VWF^–/– mice continued bleeding for episodes lasting more than 10 minutes; this is the bleeding phenotype that characterizes this animal model.¹²  VWF^–/– mice receiving 100 μg eGFP cDNA showed no effect on bleeding time when tested at 24, 48, or 72 hours. Administration of 10 μg or50 μg VWF cDNA also had no effect on bleeding time at 24 hours, but by 48 hours after injection, bleeding time in the animals receiving 50 μg VWF cDNA was normalized. Administration of 100 μg or 250 μg VWF cDNA resulted in the normalization of bleeding time by 24 hours and persisted until at least 72 hours.