Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential

Helen Bolton, Sarah J. L. Graham, Niels Van der Aa, Parveen Kumar, Koen Theunis, Elia Fernandez Gallardo, Thierry Voet and Magdalena Zernicka-Goetz ()
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Helen Bolton: Development and Neuroscience and Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Sarah J. L. Graham: Development and Neuroscience and Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Niels Van der Aa: University of Leuven, KU Leuven
Parveen Kumar: University of Leuven, KU Leuven
Koen Theunis: University of Leuven, KU Leuven
Elia Fernandez Gallardo: University of Leuven, KU Leuven
Thierry Voet: University of Leuven, KU Leuven
Magdalena Zernicka-Goetz: Development and Neuroscience and Gurdon Institute, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

Date: 2016
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DOI: 10.1038/ncomms11165

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