Conditional inactivation of ADAM10 results in MPD. (A) Gross morphology of spleen from 8-week-old control and Adam10/Mx1 mice injected with polyinosinic:polycytidylic acid at 4 weeks before euthanasia (scale bar represents 1 cm). (B) Spleen/body weight ratios and total cell counts in the spleen. Bars indicate mean ± SD (n = 5). (C) H&E staining of sections of the spleen (i-iv; bars represent 200 μm [i and ii] and 50 μm [iii and iv]), liver (v and vi; bar represents 100 μm), and metatarsi (vii and viii; bar represents 250 μm) from 12-week-old control and Adam10/Mx1 mice injected with polyinosinic:polycytidylic acid at 8 weeks before euthanasia. The spleen of Adam10/Mx1 mice shows an increase in the number of myeloid cells, as well as megakaryocytes (arrowheads) in the red pulp (i-iv). In addition, granulocytic cells are present in the liver of Adam10/Mx1 mice, which indicates extramedullary hematopoiesis (v and vi arrowheads). The metatarsi of the mutant mice are filled with hematopoietic cells, whereas the BM cavity of control animals is filled with adipose cells (vii and viii arrowheads). (D) Complete blood counts for control and Adam10/Mx1 mice. Bars indicate mean ± SD (n = 4); HCT, hematocrit; HGB, hemoglobin; RBC, red blood cells; WBC, white blood cells; and PLT, platelets. (E) Flow cytometric analysis of peripheral blood. Bars indicate mean ± SD (n = 4). (F) Flow cytometric analysis of CD3e⁺, and B220⁺ cells in the spleen and Gr-1⁺ CD11b⁺ cells in the BM from control and Adam10/Mx1 mice (boxed areas). (G) Absolute cell numbers of Gr-1⁺ CD11b⁺ cells in the BM and CD3e⁺ and Gr-1⁺ CD11b⁺ cells in the spleen. Bars indicate mean ± SD (n = 4). (H) Flow cytometric analysis of the KSL cell populations in the BM and spleen of control and Adam10/Mx1 mice. Boxed areas indicate KSL cells. (I) Absolute numbers of KSL cells in the BM and spleen. Bars indicate mean ± SD (n = 3). (J) Numbers of colony-forming units (CFUs) per 1 × 10⁵ splenocytes and 1 × 10⁴ BM cells, respectively. Bars indicate mean ± SD (n = 5). The flow cytometric analysis shown here is a representative result of 3 independent experiments. (K) Transcript levels of Hes1, Hey1, and Hey2 in the spleen of control and Adam10/Mx1 mice. t test: *P < .05, **P < .005.