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Knockout rats generated by embryo microinjection of TALENs

Nature Biotechnology volume 29, pages 695–696 (2011)Cite this article

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To the Editor:

The recent description of highly active transcription activator-like effector nucleases (TALENs)1 prompted us to explore their utility for in vivo genetic engineering in the laboratory rat. The rat is a valuable experimental animal because of its suitability for modeling human disease and toxicology. Zinc-finger nuclease (ZFN) technology and the isolation of rat embryonic stem cells have enabled targeted modifications of the rat genome2,3,4,5. Recently, Xanthomonas-derived transcription activator-like (TAL) effector proteins have elicited much interest because of their apparently simple rules for sequence-specific DNA recognition6,7. Several investigators have fused the FokI nuclease domain to TAL effector proteins to create TALENs1,8,9,10,11,12. However, only optimal truncation of the TAL effector protein allowed high-frequency gene disruption of endogenous loci and targeted DNA integration1,13,14. Here we use TALENs to disrupt the rat IgM locus, creating heritable mutations that eliminate IgM function. Our results establish the use of TALEN technology for in vivo gene knockout in mammals.

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Figure 1: Design and assay of TALENs that target rat IgM locus.

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Authors and Affiliations

  1. INSERM UMR 643, Nantes, France

    Laurent Tesson, Claire Usal, Séverine Ménoret, Séverine Remy & Ignacio Anegon

  2. Platform Transgenic Rats Nantes IBiSA-CNRS, CHU Nantes, Nantes

    Laurent Tesson, Claire Usal, Séverine Ménoret, Séverine Remy & Ignacio Anegon

  3. Université de Nantes,

    Laurent Tesson, Claire Usal, Séverine Ménoret, Séverine Remy & Ignacio Anegon

  4. Sangamo Biosciences, Richmond, California, USA

    Elo Leung, Brett J Niles, Yolanda Santiago, Anna I Vincent, Xiangdong Meng, Lei Zhang, Philip D Gregory & Gregory J Cost

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  1. Laurent Tesson
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Correspondence to Ignacio Anegon or Gregory J Cost.

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Competing interests

E.L., B.J.N., Y.S., A.I.V., X.M., L.Z., P.D.G, and G.J.C. are employees of Sangamo BioSciences. Sangamo BioSciences provided financial support for research in I.A.'s laboratory. Sangamo BioSciences has filed a patent application on the basis of these results.

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Supplementary Figures 1–3, Supplementary Tables 1–4, Supplementary Sequences and Supplementary Methods (PDF 5808 kb)

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Tesson, L., Usal, C., Ménoret, S. et al. Knockout rats generated by embryo microinjection of TALENs. Nat Biotechnol 29, 695–696 (2011). https://doi.org/10.1038/nbt.1940

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