RNA sequencing-based identification of aberrant imprinting in cloned mice

Hiroaki Okae, Shogo Matoba, Takeshi Nagashima, Eiji Mizutani, Kimiko Inoue, Narumi Ogonuki, Hatsune Chiba, Ryo Funayama, Satoshi Tanaka, Nobuo Yaegashi, Keiko Nakayama, Hiroyuki Sasaki, Atsuo Ogura, Takahiro Arima

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    34 Citations (Scopus)

    Abstract

    Animals cloned by somatic cell nuclear transfer (SCNT) provide a unique model for understanding the mechanisms of nuclear epigenetic reprograming to a state of totipotency. Though many phenotypic abnormalities have beendemonstrated in cloned animals, the underlyingmechanismsare not well understood. In this study,weperformed transcriptome-wide allelic expression analyses in brain and placental tissues of cloned mice. We found that Gab1, Sfmbt2 and Slc38a4showed loss of imprinting in all cloned mice analyzed, which might be involved in placentomegaly of cloned mice. These three genes did not require de novoDNAmethylation in growing oocytes for the establishment of imprinting, implying the involvement of a de novoDNAmethylation-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.

    Original languageEnglish
    Article numberddt495
    Pages (from-to)992-1001
    Number of pages10
    JournalHuman Molecular Genetics
    Volume23
    Issue number4
    DOIs
    Publication statusPublished - Feb 1 2014

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Genetics
    • Genetics(clinical)

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  • Cite this

    Okae, H., Matoba, S., Nagashima, T., Mizutani, E., Inoue, K., Ogonuki, N., Chiba, H., Funayama, R., Tanaka, S., Yaegashi, N., Nakayama, K., Sasaki, H., Ogura, A., & Arima, T. (2014). RNA sequencing-based identification of aberrant imprinting in cloned mice. Human Molecular Genetics, 23(4), 992-1001. [ddt495]. https://doi.org/10.1093/hmg/ddt495