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

Nat Commun. 2016 Mar 29;7:11165. doi: 10.1038/ncomms11165.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy*
  • Animals
  • Blastocyst / cytology*
  • Cell Count
  • Cell Lineage / genetics*
  • Chromosome Segregation / drug effects
  • Chromosomes, Mammalian / drug effects
  • Embryo Implantation
  • Female
  • Fertilization in Vitro
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mitosis / drug effects
  • Models, Genetic*
  • Morpholines / pharmacology
  • Mosaicism*
  • Protein Kinase Inhibitors / pharmacology
  • Purines / pharmacology
  • Zygote / cytology
  • Zygote / drug effects

Substances

  • Morpholines
  • Protein Kinase Inhibitors
  • Purines
  • 2-(4-morpholinoanilino)-6-cyclohexylaminopurine