In vivo analysis of wt-VWF and mutants p.L1696R and p.P1824H
| cDNA injected . | VWF:Ag (homozygous expression) . | VWF:Ag (heterozygous expression) . | Fold increase . | Formation of thrombi >30 µm . | Occlusion . | ||
|---|---|---|---|---|---|---|---|
| Veins . | Arterioles . | Veins . | Arterioles . | ||||
| wt-huVWFmuA1 | 259 ± 26% | NA | NA | 7/7 | 7/7 | 6/7 | 7/7 |
| p.L1696R-huVWFmuA1 ± wt-huVWFmuA1 | <5% | 94 ± 66% | 26 | 7/7 | 7/7 | 5/7 | 2/7* |
| p.P1824H-huVWFmuA1 ± wt-huVWFmuA1 | <5% | 43 ± 22% | 8 | 6/6 | 5/6 | 4/6 | 0/6** |
| cDNA injected . | VWF:Ag (homozygous expression) . | VWF:Ag (heterozygous expression) . | Fold increase . | Formation of thrombi >30 µm . | Occlusion . | ||
|---|---|---|---|---|---|---|---|
| Veins . | Arterioles . | Veins . | Arterioles . | ||||
| wt-huVWFmuA1 | 259 ± 26% | NA | NA | 7/7 | 7/7 | 6/7 | 7/7 |
| p.L1696R-huVWFmuA1 ± wt-huVWFmuA1 | <5% | 94 ± 66% | 26 | 7/7 | 7/7 | 5/7 | 2/7* |
| p.P1824H-huVWFmuA1 ± wt-huVWFmuA1 | <5% | 43 ± 22% | 8 | 6/6 | 5/6 | 4/6 | 0/6** |
VWF-deficient mice were injected hydrodynamically with wt- or mutant-huVWFmuA1 cDNA or with a 50:50 mix of both cDNAs. Four days after injection, mice expressing heterozygous VWF were tested in a FeCl3-induced thrombosis model. Thrombus formation and vessel occlusion was recorded for each vessel, vein, or arteriole. Statistical analysis was performed using 2-tailed χ-square test. Antigen levels are in comparison with normal pooled human plasma. Fold increase refers to the increase in Ag levels in the heterozygous expression compared with homozygous expression.
NA, not applicable.
*0.0053, **0.0003 compared with wt-huVWFmuA1.