Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2.
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.
Dobles
M
M
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Liberal
V
V
Scott
M L
ML
Benezra
R
R
Sorger
P K
PK
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020090:Chromosome Segregation; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D064246:Mad2 Proteins; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017386:Sequence Homology, Amino Acid
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C577699:Mad2l2 protein, mouse; D009687:Nuclear Proteins