Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2
Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2
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DOI：
10.1016/s0092-8674(00)80875-2
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发表时间：
2000-06-09
期刊：
影响因子：
64.5
通讯作者：
Sorger, PK
中科院分区：
文献类型：
--
作者：
Dobles, M;Liberal, V;Sorger, PK
染色体分离在后期开始，通过纺锤体组装检查点连接到中期染色体-微管附着的完成。为了确定有丝分裂检查点蛋白Mad2在正常细胞分裂和有丝分裂出错时的功能，我们在小鼠中敲除了Mad2。我们发现缺乏Mad2的E5.5胚胎细胞，像Mad2酵母一样，正常生长，但在纺锤体断裂时不能停止。在E6.5时，外胚层细胞开始快速细胞分裂，缺少检查点导致广泛的染色体错分离和凋亡。相反，有丝分裂后滋养层巨细胞在没有Mad2的情况下存活。因此，纺锤体组装检查点对于有丝分裂小鼠细胞中准确的染色体分离和胚胎存活是必需的，即使在没有纺锤体损伤的情况下也是如此。
The initiation of chromosome segregation at anaphase is linked by the spindle assembly checkpoint to the completion of chromosome-microtubule attachment during metaphase. To determine the function of the mitotic checkpoint protein Mad2 during normal cell division and when mitosis goes awry, we have knocked out Mad2 in mice. We find that E5.5 embryonic cells lacking Mad2, like mad2 yeast, grow normally but are unable to arrest in response to spindle disruption. At E6.5, the cells of the epiblast begin rapid cell division and the absence of a checkpoint results in widespread chromosome missegregation and apoptosis. In contrast, the postmitotic trophoblast giant cells survive without Mad2. Thus, the spindle assembly checkpoint is required for accurate chromosome segregation in mitotic mouse cells, and for embryonic viability, even in the absence of spindle damage.