Figure 7.
Endothelium-specific E1841K mutant mice show normal platelets while megakaryocyte-specific E1841K mutant mice show platelet abnormalities characteristic of MYH9-RD. (A) Live-cell images of proplatelet formation from isolated megakaryocytes. Scale bars represent 20 μm. (B) Wright-Giemsa–stained blood smears from cre-, Tie2-cre/E1841Kflox/+, and Tie2-cre/E1841Kflox/flox mice show normal size platelets (black arrows), while blood smears from PF4-cre/E1841Kflox/+ and PF4-cre/E1841Kflox/flox mice show abnormally large platelets (red arrow). (C) Mean platelet volumes of circulating platelets. Results represent mean ± SD. MPVs of cre-/E1841Kflox/flox: 7.86 ± 1.09 fL (n = 16); PF4-cre/E1841Kflox/+: 9.44 ± 0.58 fL (n = 16); PF4-cre/E1841Kflox/flox: 11.18 ± 3.14 fL (n = 16); Tie2-cre/E1841Kflox/+: 7.88 ± 0.94 fL (n = 16); and Tie2-cre/E1841Kflox/flox: 8.04 ± 0.22 fL (n = 16) (NS > 0.05; *P < .05; **P < .01). (D) Platelet diameters measured from peripheral blood smears. Platelet diameters (mean ± SD) of cre-/E1841Kflox/flox: 2.45 ± 0.58 μm (n = 150); PF4-cre/E1841Kflox/+: 3.02 ± 0.67 μm (n = 150); PF4-cre/E1841Kflox/flox: 3.66 ± 1.14 μm (n = 150); Tie2-cre/E1841Kflox/+: 2.59 ± 0.57 μm (n = 150); and Tie2-cre/E1841Kflox/flox: 2.51 ± 0.59 μm (n = 150) (NS > 0.05; *P < .05; **P < .01). (E) Circulating platelet counts from peripheral blood. Results represent mean ± SD. Circulating platelet counts of cre-/E1841Kflox/flox: 954.75 ± 152.63 K/μL (n = 16); PF4-cre/E1841Kflox/+: 764.12 ± 175.43 K/μL (n = 16); PF4-cre/E1841Kflox/flox: 522.19 ± 154.08 K/μL (n = 16); Tie2-cre/E1841Kflox/+: 1029.56 ± 322.01 K/μL (n = 16); and Tie2-cre/E1841Kflox/flox: 1124.44 ± 176.18 K/μL (n = 16) (NS > 0.05; *P < .05; **P < .01). (F) Clot retraction test 5 hours after stimulation (n = 5 per genotype). NS, not significant.

Endothelium-specific E1841K mutant mice show normal platelets while megakaryocyte-specific E1841K mutant mice show platelet abnormalities characteristic of MYH9-RD. (A) Live-cell images of proplatelet formation from isolated megakaryocytes. Scale bars represent 20 μm. (B) Wright-Giemsa–stained blood smears from cre-, Tie2-cre/E1841Kflox/+, and Tie2-cre/E1841Kflox/flox mice show normal size platelets (black arrows), while blood smears from PF4-cre/E1841Kflox/+ and PF4-cre/E1841Kflox/flox mice show abnormally large platelets (red arrow). (C) Mean platelet volumes of circulating platelets. Results represent mean ± SD. MPVs of cre-/E1841Kflox/flox: 7.86 ± 1.09 fL (n = 16); PF4-cre/E1841Kflox/+: 9.44 ± 0.58 fL (n = 16); PF4-cre/E1841Kflox/flox: 11.18 ± 3.14 fL (n = 16); Tie2-cre/E1841Kflox/+: 7.88 ± 0.94 fL (n = 16); and Tie2-cre/E1841Kflox/flox: 8.04 ± 0.22 fL (n = 16) (NS > 0.05; *P < .05; **P < .01). (D) Platelet diameters measured from peripheral blood smears. Platelet diameters (mean ± SD) of cre-/E1841Kflox/flox: 2.45 ± 0.58 μm (n = 150); PF4-cre/E1841Kflox/+: 3.02 ± 0.67 μm (n = 150); PF4-cre/E1841Kflox/flox: 3.66 ± 1.14 μm (n = 150); Tie2-cre/E1841Kflox/+: 2.59 ± 0.57 μm (n = 150); and Tie2-cre/E1841Kflox/flox: 2.51 ± 0.59 μm (n = 150) (NS > 0.05; *P < .05; **P < .01). (E) Circulating platelet counts from peripheral blood. Results represent mean ± SD. Circulating platelet counts of cre-/E1841Kflox/flox: 954.75 ± 152.63 K/μL (n = 16); PF4-cre/E1841Kflox/+: 764.12 ± 175.43 K/μL (n = 16); PF4-cre/E1841Kflox/flox: 522.19 ± 154.08 K/μL (n = 16); Tie2-cre/E1841Kflox/+: 1029.56 ± 322.01 K/μL (n = 16); and Tie2-cre/E1841Kflox/flox: 1124.44 ± 176.18 K/μL (n = 16) (NS > 0.05; *P < .05; **P < .01). (F) Clot retraction test 5 hours after stimulation (n = 5 per genotype). NS, not significant.

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