Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system

Adam J. Dupuy, Keiko Akagi, David A. Largaespada, Neal G. Copeland, Nancy A. Jenkins

Research output: Contribution to journalArticlepeer-review

389 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)221-226
Number of pages6
JournalNature
Volume436
Issue number7048
DOIs
StatePublished - Jul 14 2005

Bibliographical note

Funding Information:
Acknowledgements We thank D. Swing and R. Koogle for generating the T2/Onc2 transgenic mice and maintaining all mouse strains, and E. Southon and S. Reed for generating mice carrying the RosaSB knock-in allele. This research is supported by the Department of Health and Human Services, National Institutes of Health and the National Cancer Institute.

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