Figure 3.
Loss of α4A- and β1-tubulins severely impairs hemostatic and thrombotic responses in vivo. (A) Percentage of bleeders over time following a 3-mm tail-tip amputation for WT, KOA4A (A4A), KOB1 (B1), and DKO mice and romiplostim-treated DKO mice (DKO+R). Results are represented as Kaplan-Meier survival curves. For romiplostim-treated animals, mice were administered a single dose (100 μg/kg) 6 days prior to the experiment. N > 6 per group. Statistical analysis was conducted by the log-rank test. (B) Representative fluorescence micrographs of thrombi formed at 14, 24, and 40 minutes after topical application of FeCl3 to the carotid artery of WT, KOA4A (A4A), KOB1 (B1), and DKO mice. Platelets were labeled by 3,3'-dihexyloxacarbocyanine iodide injection. (C) Thrombus area quantification after topical application of FeCl3 to the carotid artery of WT, KOA4A (A4A), KOB1 (B1), and DKO mice. Results are expressed in mm2 as a function of time (minutes). N > 5 per strain. (D) Representative scanning electron micrographs of WT and DKO thrombi in transsectioned carotid arteries that have been fixed 7 minutes after topical application of FeCl3. (E) Percentage of survival over time of WT, KOA4A (A4A), KOB1 (B1), and DKO mice in a venous thromboembolism model following an injection in the jugular vein of a mixture of collagen (0.8 mg/kg) and adrenaline (60 μg/kg). Results are represented as Kaplan-Meier survival curves. N > 3 per group. Statistical analysis was conducted by the log-rank test. Scale bars, 300 μm (B) and 2 μm (D).