Subaquatic bleeding time, platelet concentrations, and bone marrow histology showing reduced megakaryocyte numbers. Subaquatic bleeding time was measured to assess hemostasis (A). Apparently reduced platelet numbers in transgenic mice (B) were calculated to be in the same range or even increased in comparison with wild-type mice when the highly reduced distribution volume of platelets; that is, the plasma fraction, was taken into account (C). Sternal bone marrow was quantified for the presence of megakaryocytes per high-power (× 400) visual field (D) showing a progressive reduction of megakaryocyte numbers with increasing age (n = 5 per group). *P < .01, ^#P < .001, compared with age-matched wild-type controls. Panels E (wild-type) and F (transgenic) illustrate the reduced number of megakaryocytes in 8-month-old transgenic mice compared with age-matched wild-type controls. M indicates megakaryocyte. All sections were stained with hematoxylin and eosin (original magnification, × 400), scale 20 μm.