Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis

Bub3 is a conserved component of the mitotic spindle assembly complex. The protein is essential for early development in Bub3 gene-disrupted mice, evi dent from their failure to survive beyond day 6.5-7.5 postcoitus (pc). Bub3 null embryos appear normal up to day 3.5 pc but accumulate mitotic errors from days 4.5-6.5 pc in the form of micronuclei, chromatin bridging, laggin g chromosomes, and irregular nuclear morphology. Null embryos treated with a spindle-depolymerising agent fail to arrest in metaphase and show an incr ease in mitotic disarray. The results confirm Bub3 as a component of the es sential spindle checkpoint pathway that operates during early embryogenesis .