The SAC is not required in budding yeast, perhaps because these cells enter mitotic progression with correct attachment of kinetochores to microtubules. However, in vertebrate cells SAC is essential for normal mitotic progression. Mice with homozygous null mutations in the SAC die at a very early stage of embryogenesis. Thus our understanding of SAC in eukaryotic cells has largely been restricted to the analysis of mice with heterozygous mutations which harbor one null and one wild-type allele. Heterozygous mice can develop normally but are predisposed to spontaneous tumor development. Mice with an expression level of approximate 11% BubR1 are not predisposed to tumors but exhibit premature aging ITSA-1 phenotypes, and fibroblasts isolated from these mice showed SAC defects and aneuploidy. Heterozygotes with Bub3 mutants also age prematurely. Furthermore, mouse embryo fibroblasts heterozygous for Bub3, BubR1 and Mad2 all show SAC defects and high levels of aneuploidy. Indeed, in HCT166 cells, reduction of Mad2 protein levels to 70% results in complete abrogation of SAC. The initial suggestion that SAC might not exist in vertebrate oocytes which would explain the high incidence of aneuploidy comes from studies of XO mice, which have only one X chromosome but are fertile and phenotypically female. However, this study has been challenged by the finding that microtubule inhibitors such as nocodazole can block polar body extrusion and the onset of securin proteolysis. Furthermore, injection of Mad2, Bub3 or BubR1 morpholinos, or expression of dominant negative Mad2, Bub1 or BubR1 by microinjection of mRNA encoding the mutant protein lacking the kinase domain leads to an acceleration of meiosis, with high levels of chromosome missegregation and aneuploidy. These results demonstrate that SAC does exist and detects attachment errors to microtubules in mouse oocytes. Mistakes in chromosome segregation or distribution may result in aneuploid embryo formation, which causes spontaneous abortion, genetic diseases, or embryo death. 16-Epiestriol Embryonic aneuploidies are produced when abnormal chromosomes or their abnormal segregation are present in gametes or early stage embryos. To date, there is no direct evidence showing that SAC is required for the regulation of mitotic cell cycle progression during preimplantation development.