RNA sequencing-based identification of aberrant imprinting in cloned mice

Hum Mol Genet. 2014 Feb 15;23(4):992-1001. doi: 10.1093/hmg/ddt495. Epub 2013 Oct 8.


Animals cloned by somatic cell nuclear transfer (SCNT) provide a unique model for understanding the mechanisms of nuclear epigenetic reprogramming to a state of totipotency. Though many phenotypic abnormalities have been demonstrated in cloned animals, the underlying mechanisms are not well understood. In this study, we performed transcriptome-wide allelic expression analyses in brain and placental tissues of cloned mice. We found that Gab1, Sfmbt2 and Slc38a4 showed loss of imprinting in all cloned mice analyzed, which might be involved in placentomegaly of cloned mice. These three genes did not require de novo DNA methylation in growing oocytes for the establishment of imprinting, implying the involvement of a de novo DNA methylation-independent mechanism. Loss of Dlk1-Dio3 imprinting was also observed in nearly half of cloned mouse embryos and showed a strong correlation with embryonic lethality. Our findings are essential to understand the underlying mechanisms of developmental abnormalities of cloned animals. We also emphasize that particular attention should be paid to specific imprinted genes for therapeutic and agricultural applications of SCNT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Transport System A / genetics
  • Animals
  • Base Sequence
  • Brain / metabolism
  • Cloning, Organism*
  • Female
  • Genomic Imprinting*
  • Iodide Peroxidase / genetics
  • Mice
  • Phosphoproteins / genetics
  • Placenta / metabolism
  • Pregnancy
  • Repressor Proteins
  • Sequence Analysis, RNA
  • Transcription Factors / genetics
  • Transcriptome


  • Adaptor Proteins, Signal Transducing
  • Amino Acid Transport System A
  • Gab1 protein, mouse
  • Phosphoproteins
  • Repressor Proteins
  • Sfmbt2 protein, mouse
  • Slc38a4 protein, mouse
  • Transcription Factors
  • iodothyronine deiodinase type III
  • Iodide Peroxidase