Figure 4

Thrombocytopaenia in Bclx-deficient mice is not exacerbated by BCL-2 inhibition. Platelet (a) and bone marrow megakaryocyte counts (b) 6 and 24 h post oral administration of the BCL-2-selective BH3 mimetic ABT-199 (A-199) 100 mg/kg or vehicle control. n=3–4 mice per group, except Bclx^Pf4Δ/Pf4Δ 24 h vehicle where n=2. Platelet counts are shown on a log scale. (c) Platelet counts (log scale) in Bcl2^Pf4Δ/Pf4Δ Bclx^Pf4Δ/Pf4Δ, Bcl2^+/+ Bclx^Pf4Δ/Pf4Δ and floxed control mice at 7–10 weeks of age. (d) Platelet survival curves in Bcl2^Pf4Δ/Pf4Δ Bclx^Pf4Δ/fl and Bcl2^Pf4Δ/fl Bclx^Pf4Δ/fl mice. Platelets were labelled via i.v. injection of a DyLight 488-conjugated anti-CD42c mAb. n=4 mice per genotype. Time 0 (100%) was set at 1 h post injection. (e) Numbers of morphologically recognisable megakaryocytes in H&E-stained bone marrow and spleen sections. n=8–17 mice per genotype. (f) Ploidy distribution profile of CD41⁺ bone marrow cells, as determined by flow cytometry. n=4 mice per genotype. *P<0.05; **P<0.005; ***P<0.001. Data represent mean±S.D.