Figure 3.
Inducible Hippo kinase deletion in the adult mouse hematopoietic system recapitulates MDS and MPN phenotypes. Recipient mice analyzed in this figure were derived from cells of the following genotypes: Stk4f/fStk3f/f;Mx1-Cre+ (Stk4Δ/ΔStk3Δ/Δ, red), Stk4f/+Stk3f/+;Mx1-Cre+ (Stk4Δ/+Stk3Δ/+, blue), and Stk4f/fStk3f/f;Mx1-Cre− (Stk4+/+Stk3+/+, green); n = 9 mice per genotype. (A) Experimental schematic depicting generation of bone marrow chimeras and pIpC treatment to induce hematopoietic-specific gene deletion for the indicated genotypes. (B) Gene expression for Stk4 and Stk3 measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in flow-sorted Lin− cKIT+ hematopoietic progenitor cells derived from 2 representative mice of the indicated genotypes, 2 weeks after completion of pIpC treatment. Peripheral blood white blood cell (WBC) counts (C); peripheral blood platelet counts (D); representative spleens from mice of the indicated genotypes, 6 weeks after pIpC treatment (E); peripheral blood granulocyte counts (F); peripheral blood granulocyte frequencies (G); and peripheral blood MPV (H). (I) Representative Wright-Giemsa–stained peripheral blood smears from mice of the indicated genotypes, 6 weeks after pIpC treatment. Arrowheads indicate abnormally large platelets. Scale bar, 50 μm. (J) Peripheral blood red blood cell (RBC) counts. Data are representative of 2 independent experiments. Homozygous and heterozygous groups were independently tested for statistical significance against controls by multiple t tests with the Holm-Sidak correction. *P < .05, **P < .01, ***P < .001.