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Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system

Author

Listed:
  • Adam J. Dupuy

    (Center for Cancer Research)

  • Keiko Akagi

    (Center for Cancer Research)

  • David A. Largaespada

    (University of Minnesota)

  • Neal G. Copeland

    (Center for Cancer Research)

  • Nancy A. Jenkins

    (Center for Cancer Research)

Abstract

Transposons have provided important genetic tools for functional genomic screens in lower eukaryotes but have proven less useful in higher eukaryotes because of their low transposition frequency. Here we show that Sleeping Beauty (SB), a member of the Tc1/mariner class of transposons, can be mobilized in mouse somatic cells at frequencies high enough to induce embryonic death and cancer in wild-type mice. Tumours are aggressive, with some animals developing two or even three different types of cancer within a few months of birth. The tumours result from SB insertional mutagenesis of cancer genes, thus facilitating the identification of genes and pathways that induce disease. SB transposition can easily be controlled to mutagenize any target tissue and can therefore, in principle, be used to induce many of the cancers affecting humans, including those for which little is known about the aetiology. The uses of SB are also not restricted to the mouse and could potentially be used for forward genetic screens in any higher eukaryote in which transgenesis is possible.

Suggested Citation

  • Adam J. Dupuy & Keiko Akagi & David A. Largaespada & Neal G. Copeland & Nancy A. Jenkins, 2005. "Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system," Nature, Nature, vol. 436(7048), pages 221-226, July.
    • Handle: RePEc:nat:nature:v:436:y:2005:i:7048:d:10.1038_nature03691
    DOI: 10.1038/nature03691
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    Cited by:

    1. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Kana Shimomura & Naoko Hattori & Naoko Iida & Yukari Muranaka & Kotomi Sato & Yuichi Shiraishi & Yasuhito Arai & Natsuko Hama & Tatsuhiro Shibata & Daichi Narushima & Mamoru Kato & Hiroyuki Takamaru &, 2023. "Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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