Cause of death for BUBR1-null embryos.BUBR1-null embryos die of apoptosis. Postimplantation mouse embryos at E8.5 were fixed, embedded in paraffin, and sectioned transversely. Neighboring sections were either stained with hematoxylin-eosin (panel A) or subjected to the TUNEL technique (panel B), and were then examined at low (scale bar = 0.2 μm) and high (scale bar = 5 nm) magnification (upper and lower panels, respectively). Arrowheads indicate embryos or embryonic remnants. Attempts to confirm the genotypes of the abnormally developed or resorbed embryos were rendered difficult by contamination of tissue from the mother. The BUBR1^–/– designation of the embryo shown was thus presumed. Gross morphologic examination, however, demonstrated that about one fourth of the embryos resulting from BUBR1^+/– intercrosses either developed abnormally or were resorbed (Table 1) and that atrophic embryos were rarely observed to result from intercrosses of wild-type animals, thus supporting the presumptive genotyping.