Ultrastructural studies of cleavage stage t¹²/t¹² mouse embryos

A statistical study of embryos obtained from both spontaneously ovulated and superovulated +/t 12 females, mated inter se , shows that the range of the lethal phenocritical period of the t 12 allele in a homozygous condition is from the 8–12 cell stage to the early blastocyst stage. The majority of t 12 homozygotes are developmentally arrested as late morula and the nuclei of these embryos contain lipid droplets and fibrillo‐granular bodies. These same inclusions are found in other t 12 embryos which are developmentally arrested either earlier or later than the late morula stage and distinguish 30–40% of the embryos (presumably t 12 homozygotes) from their litter‐mates at the 2‐ and 4‐cell stages. Ultrastructural‐cytochemical studies of the fibrillo‐granular bodies show that the fibrillar areas are sensitive to pepsin and the granules to ribonuclease and are thus structurally and chemically similar to definitive nucleoli. Binucleate cells are also present in a high frequency of t 12 homozygous embryos. This condition is considered an additional phenotypic expression of the genotype. Prior to developmental arrest, the nuclear and cytoplasmic organelles of t 12 embryos do not differ from those of similarly staged litter‐mates or control +/+ embryos. Homozygous mutant embryos examined shortly following developmental arrest contain cells ranging from structurally normal to degenerative. Asynchronous cell death is common to all t 12 homozygous embryos. A chronological description of degenerative cellular changes is presented.