Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system
- PMID: 16015321
- DOI: 10.1038/nature03691
Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system
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.
Comment in
-
Cancer biology: Sleeping Beauty awakens.Nature. 2005 Jul 14;436(7048):184-6. doi: 10.1038/436184a. Nature. 2005. PMID: 16015313 No abstract available.
-
Transposons reanimated in mice.Cell. 2005 Aug 12;122(3):322-5. doi: 10.1016/j.cell.2005.07.024. Cell. 2005. PMID: 16096053 Review.
Similar articles
-
Insertional engineering of chromosomes with Sleeping Beauty transposition: an overview.Methods Mol Biol. 2011;738:69-85. doi: 10.1007/978-1-61779-099-7_5. Methods Mol Biol. 2011. PMID: 21431720 Review.
-
Cancer gene discovery in solid tumours using transposon-based somatic mutagenesis in the mouse.Nature. 2005 Jul 14;436(7048):272-6. doi: 10.1038/nature03681. Nature. 2005. PMID: 16015333
-
Cancer biology: Sleeping Beauty awakens.Nature. 2005 Jul 14;436(7048):184-6. doi: 10.1038/436184a. Nature. 2005. PMID: 16015313 No abstract available.
-
Sleeping beauty--a mouse model for all cancers?Cancer Lett. 2012 Apr 1;317(1):1-8. doi: 10.1016/j.canlet.2011.11.006. Epub 2011 Nov 10. Cancer Lett. 2012. PMID: 22079740 Review.
-
Insertional mutagenesis of the mouse germline with Sleeping Beauty transposition.Methods Mol Biol. 2008;435:109-25. doi: 10.1007/978-1-59745-232-8_8. Methods Mol Biol. 2008. PMID: 18370071
Cited by
-
SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research.Front Oncol. 2021 Apr 23;11:667189. doi: 10.3389/fonc.2021.667189. eCollection 2021. Front Oncol. 2021. PMID: 33968774 Free PMC article. Review.
-
A genome-scale in vivo loss-of-function screen identifies Phf6 as a lineage-specific regulator of leukemia cell growth.Genes Dev. 2015 Mar 1;29(5):483-8. doi: 10.1101/gad.254151.114. Genes Dev. 2015. PMID: 25737277 Free PMC article.
-
In vivo functional screening for systems-level integrative cancer genomics.Nat Rev Cancer. 2020 Oct;20(10):573-593. doi: 10.1038/s41568-020-0275-9. Epub 2020 Jul 7. Nat Rev Cancer. 2020. PMID: 32636489 Review.
-
A most formidable arsenal: genetic technologies for building a better mouse.Genes Dev. 2020 Oct 1;34(19-20):1256-1286. doi: 10.1101/gad.342089.120. Genes Dev. 2020. PMID: 33004485 Free PMC article. Review.
-
A recellularized human colon model identifies cancer driver genes.Nat Biotechnol. 2016 Aug;34(8):845-51. doi: 10.1038/nbt.3586. Epub 2016 Jul 11. Nat Biotechnol. 2016. PMID: 27398792 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
