Figure 2
Figure 2. Peripheral blood parameters in transgenic mice and controls. (A) Hemoglobin, platelets, and neutrophils were determined in controls and double transgenic mice (left half of diagrams) or in mice transplanted with retrovirally transduced bone marrow (right half of diagrams). Controls, wild-type, or single transgenic mice (n = 19); VavCre;FF1 double transgenic mice (age 10-12 weeks, n = 6); MxCre;FF1 double transgenic mice (10-12 weeks after 3 × pIpC injection, n = 11); Tx controls, mice transplanted with bone marrow cells transduced with empty vector or wild-type Jak2 (8 weeks after transplantation, n = 12); pMSCV-hV617F, mice transplanted with bone marrow transduced with human JAK2-V617F (8 weeks after transplantation, n = 9); pMSCV-mV617F, mice transplanted with bone marrow transduced with mouse Jak2-V617F (8 weeks after transplantation, n = 9). Boxes represent the interquartile range that contains 50% of the values, the horizontal line in the box marks the median, and bars indicate the range of values. Asterisks indicate significant differences compared with controls (Mann-Whitney test, P < .05). (B) Time course of blood parameters in VavCre;FF1, MxCre;FF1, and control mice. Blood counts of individual mice at 5-6 weeks, 10-12 weeks, and 20 weeks of age (VavCre;FF1) or after 3 × pIpC injection (MxCre;FF1) are shown. Each mouse is represented by the same symbol in all 3 graphs, and values of individual mice are connected by solid lines. Black symbols, transgenic mice; gray symbols, control mice. (C) Blood films of mice of the indicated genotypes stained with May-Grünwald-Giemsa. VavCre;FF1 mice (20 weeks) and MxCre;FF1 (20 weeks after 3 × pIpC). Note massive thrombocytosis in both mice and prominent neutrophilia in the MxCre;FF1 mouse. (D) Plasma levels of thrombopoietin (Tpo) and erythropoietin (Epo) determined by ELISA. Tpo levels were not significantly different between controls (n = 5), VavCre;FF1 mice (n = 5) and MxCre;FF1 mice (n = 3). Plasma from Mpl-deficient mice (Mpl-/-) served as a control for elevated Tpo levels. Epo plasma concentrations were determined in controls (n = 4), VavCre;FF1 mice (n = 7) and MxCre;FF1 mice (n = 4). Epo was found to be significantly lower in MxCre;FF1 mice than in VavCre;FF1 mice (Mann-Whitney test, P = .012) (E) Spleen weight in VavCre;FF1 mice (20 weeks) and in MxCre;FF1 (20 weeks after 3 × pIpC). (F) The MPD phenotype of MxCre;FF1 mice is transplantable. Bone marrow (BM) or spleen cells (SPL) derived from an MxCre;FF1 mouse (20 weeks after 3 × pIpC) or bone marrow from a wild-type (WT) mouse were transplanted into lethally irradiated C57BL/6 recipients. Blood counts were performed 10 weeks after transplantation. Dots represent the values of individual mice and horizontal lines, the mean.

Peripheral blood parameters in transgenic mice and controls. (A) Hemoglobin, platelets, and neutrophils were determined in controls and double transgenic mice (left half of diagrams) or in mice transplanted with retrovirally transduced bone marrow (right half of diagrams). Controls, wild-type, or single transgenic mice (n = 19); VavCre;FF1 double transgenic mice (age 10-12 weeks, n = 6); MxCre;FF1 double transgenic mice (10-12 weeks after 3 × pIpC injection, n = 11); Tx controls, mice transplanted with bone marrow cells transduced with empty vector or wild-type Jak2 (8 weeks after transplantation, n = 12); pMSCV-hV617F, mice transplanted with bone marrow transduced with human JAK2-V617F (8 weeks after transplantation, n = 9); pMSCV-mV617F, mice transplanted with bone marrow transduced with mouse Jak2-V617F (8 weeks after transplantation, n = 9). Boxes represent the interquartile range that contains 50% of the values, the horizontal line in the box marks the median, and bars indicate the range of values. Asterisks indicate significant differences compared with controls (Mann-Whitney test, P < .05). (B) Time course of blood parameters in VavCre;FF1, MxCre;FF1, and control mice. Blood counts of individual mice at 5-6 weeks, 10-12 weeks, and 20 weeks of age (VavCre;FF1) or after 3 × pIpC injection (MxCre;FF1) are shown. Each mouse is represented by the same symbol in all 3 graphs, and values of individual mice are connected by solid lines. Black symbols, transgenic mice; gray symbols, control mice. (C) Blood films of mice of the indicated genotypes stained with May-Grünwald-Giemsa. VavCre;FF1 mice (20 weeks) and MxCre;FF1 (20 weeks after 3 × pIpC). Note massive thrombocytosis in both mice and prominent neutrophilia in the MxCre;FF1 mouse. (D) Plasma levels of thrombopoietin (Tpo) and erythropoietin (Epo) determined by ELISA. Tpo levels were not significantly different between controls (n = 5), VavCre;FF1 mice (n = 5) and MxCre;FF1 mice (n = 3). Plasma from Mpl-deficient mice (Mpl-/-) served as a control for elevated Tpo levels. Epo plasma concentrations were determined in controls (n = 4), VavCre;FF1 mice (n = 7) and MxCre;FF1 mice (n = 4). Epo was found to be significantly lower in MxCre;FF1 mice than in VavCre;FF1 mice (Mann-Whitney test, P = .012) (E) Spleen weight in VavCre;FF1 mice (20 weeks) and in MxCre;FF1 (20 weeks after 3 × pIpC). (F) The MPD phenotype of MxCre;FF1 mice is transplantable. Bone marrow (BM) or spleen cells (SPL) derived from an MxCre;FF1 mouse (20 weeks after 3 × pIpC) or bone marrow from a wild-type (WT) mouse were transplanted into lethally irradiated C57BL/6 recipients. Blood counts were performed 10 weeks after transplantation. Dots represent the values of individual mice and horizontal lines, the mean.

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