Related Experiment Video
Updated: Jul 11, 2026
Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos
Published on: June 14, 2012
Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2
M Dobles1, V Liberal, M L Scott
1Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Abstract:
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.
Insights
The spindle assembly checkpoint protein Mad2 is crucial for accurate chromosome segregation in mouse cells. Its absence leads to errors in cell division and embryonic death, highlighting its importance in preventing mitotic catastrophe.
Area of Science:
- Cell Biology
- Genetics
- Developmental Biology
Background:
- The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation by linking anaphase initiation to proper chromosome-microtubule attachment.
- Mad2 (mitotic arrest deficient 2) is a key protein in the SAC, but its precise role in mammalian development is not fully understood.
Purpose of the Study:
- To investigate the function of Mad2 during normal cell division and in response to mitotic stress in mice.
- To determine the consequences of Mad2 deficiency on embryonic development and chromosome segregation.
Main Methods:
- Generation of Mad2 knockout mice.
- Analysis of embryonic cell division, chromosome segregation, and apoptosis in Mad2-deficient embryos.
- Comparison of mitotic and postmitotic cell populations.
Main Results:
- Mad2-deficient embryonic cells (E5.5) divide normally but fail to arrest upon spindle disruption.
- By E6.5, epiblast cells lacking Mad2 exhibit widespread chromosome missegregation and apoptosis due to failed checkpoint control.
- Postmitotic trophoblast giant cells in Mad2-deficient embryos survive, indicating cell-type specific requirements for the SAC.
Conclusions:
- The spindle assembly checkpoint, mediated by Mad2, is essential for accurate chromosome segregation in dividing mammalian cells.
- Mad2 deficiency compromises embryonic viability by causing mitotic errors, even without external spindle damage.
- The SAC plays a critical role in maintaining genomic stability during early mouse development.
