SRSF3 depletion in MKs leads to severe thrombocytopenia without a change in MK numbers. (A) Platelet counts of heterozygous mice (KO/⁺) with a systemic Srsf3 deletion compared with wild-type mice (^+/+) (n = 6). (B) Top: Generation of a mouse model where Srsf3 is deleted in MKs (Pf4-Srsf3^Δ/Δ). Bottom: Anti-SRSF3 immunohistochemistry in Pf4-Srsf3^Δ/Δ and control bone marrow sections. (C) Platelet and red blood cell (RBC) counts of control and Pf4-Srsf3^Δ/Δ mice. (D) The total number and incidence of bone marrow MKs in control and Pf4-Srsf3^Δ/Δ mice. (E) The number of MKs of individual ploidy in control and Pf4-Srsf3^Δ/Δ bone marrow. (F) CD41, (G) CD61, and (H) c-MPL cell surface receptor expression of control and Pf4-Srsf3^Δ/Δ MKs. A histogram of a representative mouse is shown (n = 4). The proportion of events in the gate marked in the histogram (CD41/CD61/c-MPL^high) is quantified on the right. The data are presented as mean plus or minus standard error of the mean (SEM). Two-tailed unpaired Student t test in panels A and C through D; 2-way analysis of variance (ANOVA) in panels E through H. ****P ≤ .0001; ***P ≤ .001; **P ≤ .01; *P ≤ .05. Δ/Δ, Pf4-Srsf3^Δ/Δ mice; Ctrl, control.