Figure 1.
VavCre+Rxrabfl/flmice develop lethal myeloproliferative disorders. (A-C) Organ weight and counts of 2-, 5-, 12-, and 24-month-old WT and VavCre+Rxrabfl/fl mice. (A-B) Spleen and liver weigh/body weight ratios. (C) BM cellularity per femur. (D-F) Hemogram data of 2-, 5-, 12-, and 24-month-old WT and VavCre+Rxrabfl/fl mice. (D) Mean platelet counts. (E) Percentage of lymphocytes, neutrophils, and monocytes among white blood cells (WBCs). (F) Total red blood cells (RBCs). (G-J) Flow cytometry of femur and spleen homogenates from 2-, 5-, 12-, and 24-month-old WT and VavCre+Rxrabfl/fl mice. (G) Absolute numbers of erythroid progenitors (CD45−Ter119+ cells) per femur. (H) Absolute numbers of LSKs per femur. (I-J) Absolute numbers of spleen LSKs and LKs. (K) Kaplan-Meier survival plots for WT and VavCre+Rxrabfl/fl mice (n = 11-13 per genotype). (L) Representative images of femurs, spleens, and lungs of 24-month-old WT and VavCre+Rxrabfl/fl mice. (M-N) Representative images of hematoxylin and eosin (H&E)– and reticulin-stained femur sections, and of H&E-stained spleen sections from 24-month-old WT and VavCre+Rxrabfl/fl mice; yellow arrows indicate megakaryocytes. Scale bars: 500 μm (N, upper panels), 100 μm (M, upper panels; N, bottom panels), or 50 μm (M, bottom panels). (O) Representative images of H&E-stained lungs from 24-month-old WT and VavCre+Rxrabfl/fl mice; black arrows indicate alveolar hemorrhage. Scale bars: 2.5 mm (left panels) or 250 μm (middle and right panels). Data are presented as mean ± SEM: (A-F) n = 7 to 17 mice, pooled from up to 3 independent experiments per age group and genotype; (G) n = 3 to 13 mice, pooled from up to 2 independent experiments per age group and genotype; (H) n = 4 to 24 mice, pooled from up to 3 independent experiments per age group and genotype; (I) n = 5 to 12, pooled from up to 2 independent experiments per age and genotype (spleen); (J) n = 5 to 11 mice, pooled from up to 2 independent experiments per age and genotype. Significance was determined by 2-way analysis of variance followed by the Sidak multiple comparisons test (age-paired mice) (A-J) or log-rank (Mantel-Cox) test (K), and is represented as follows: ∗P ≤ .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, and ∗∗∗∗P ≤ .0001. A, alveoli; Ad, adipocytes; AS, alveolar sac; B, bronchiole.

VavCre+Rxrabfl/flmice develop lethal myeloproliferative disorders. (A-C) Organ weight and counts of 2-, 5-, 12-, and 24-month-old WT and VavCre+Rxrabfl/fl mice. (A-B) Spleen and liver weigh/body weight ratios. (C) BM cellularity per femur. (D-F) Hemogram data of 2-, 5-, 12-, and 24-month-old WT and VavCre+Rxrabfl/fl mice. (D) Mean platelet counts. (E) Percentage of lymphocytes, neutrophils, and monocytes among white blood cells (WBCs). (F) Total red blood cells (RBCs). (G-J) Flow cytometry of femur and spleen homogenates from 2-, 5-, 12-, and 24-month-old WT and VavCre+Rxrabfl/fl mice. (G) Absolute numbers of erythroid progenitors (CD45Ter119+ cells) per femur. (H) Absolute numbers of LSKs per femur. (I-J) Absolute numbers of spleen LSKs and LKs. (K) Kaplan-Meier survival plots for WT and VavCre+Rxrabfl/fl mice (n = 11-13 per genotype). (L) Representative images of femurs, spleens, and lungs of 24-month-old WT and VavCre+Rxrabfl/fl mice. (M-N) Representative images of hematoxylin and eosin (H&E)– and reticulin-stained femur sections, and of H&E-stained spleen sections from 24-month-old WT and VavCre+Rxrabfl/fl mice; yellow arrows indicate megakaryocytes. Scale bars: 500 μm (N, upper panels), 100 μm (M, upper panels; N, bottom panels), or 50 μm (M, bottom panels). (O) Representative images of H&E-stained lungs from 24-month-old WT and VavCre+Rxrabfl/fl mice; black arrows indicate alveolar hemorrhage. Scale bars: 2.5 mm (left panels) or 250 μm (middle and right panels). Data are presented as mean ± SEM: (A-F) n = 7 to 17 mice, pooled from up to 3 independent experiments per age group and genotype; (G) n = 3 to 13 mice, pooled from up to 2 independent experiments per age group and genotype; (H) n = 4 to 24 mice, pooled from up to 3 independent experiments per age group and genotype; (I) n = 5 to 12, pooled from up to 2 independent experiments per age and genotype (spleen); (J) n = 5 to 11 mice, pooled from up to 2 independent experiments per age and genotype. Significance was determined by 2-way analysis of variance followed by the Sidak multiple comparisons test (age-paired mice) (A-J) or log-rank (Mantel-Cox) test (K), and is represented as follows: ∗P ≤ .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, and ∗∗∗∗P ≤ .0001. A, alveoli; Ad, adipocytes; AS, alveolar sac; B, bronchiole.

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