Ccbe1^lacZ/lacZ embryos have reduced numbers of anuclear erythrocytes in the peripheral blood and reduced cell proliferation and increased cell death in the fetal liver. (A-D) Peripheral blood in Ccbe1^lacZ/lacZ embryos reveals a large fraction of nucleated erythrocytes when examined in H&E-stained sections (A,B) or peripheral blood smears (C,D). (E-H) Ccbe1^lacZ/lacZ fetal livers have large numbers of cells with pyknotic nuclei when examined in H&E-stained sections (E,F) and nuclear fragmentation consistent with apoptosis when examined using transmission electron microscopy (G,H). (I,J) Ccbe1^lacZ/lacZ fetal livers exhibit reduced cell proliferation as measured by immunostaining for phospho-histone H3. (K,L) Ccbe1^lacZ/lacZ fetal livers exhibit increased apoptosis as measured by immunostaining for activated caspase 3. (M) Flow cytometric analysis of Ccbe1^lacZ/lacZ fetal livers reveals large numbers of dead (top) and apoptotic (bottom) cells compared with wild-type littermate controls. * indicates fragmented, apoptotic nucleus. Scale bars represent 25 μm. aCasp 3, activated caspase 3; EB, erythroblast; MΦ, macrophage; pH3, phospho-histone H3; TEM, transmission electron microscopy.