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TALEN-mediated editing of the mouse Y chromosome

Abstract

The functional study of Y chromosome genes has been hindered by a lack of mouse models with specific Y chromosome mutations. We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes—Sry and Uty. TALEN-mediated gene editing is a useful tool for dissecting the biology of the Y chromosome.

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Figure 1: Genetic modification of Sry using TALENs.
Figure 2: Genetic modification of Uty using TALENs.

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Acknowledgements

We thank K. Ganz and R. Flannery for support with animal care and experiments. We thank Jaenisch and Page laboratory members for helpful discussions on the manuscript. A.W.C. is supported by a Croucher scholarship. D.C.P. and Y.-C.H. were supported by Howard Hughes Medical Institute. R.J., H.W., S.M., G.G.W., C.S.S. and A.W.C. were supported by US National Institutes of Health grants R37-HD045022 and R01-CA084198. T.P. was supported by US National Institutes of Health grant R01-HG000257.

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Contributions

H.W., Y.-C.H., D.C.P. and R.J. designed the experiments and wrote the manuscript. H.W., D.F.V. and A.J.B. designed TALENs. H.W. generated and tested TALENs. H.W. performed targeting experiments. C.S.S. and D.B.D. assisted with Southern blot analysis. S.M. performed tetraploid complementation experiments. Y.-C.H. and G.G.W. maintained mutant mouse colonies and performed animal-related experiments. T.P. performed FISH analysis. A.W.C. performed the off-target analysis. H.W., Y.-C.H. and G.G.W. analyzed the data.

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Correspondence to David C Page or Rudolf Jaenisch.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Figures 1–5 and Supplementary Tables 1–4 (PDF 5749 kb)

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Wang, H., Hu, YC., Markoulaki, S. et al. TALEN-mediated editing of the mouse Y chromosome. Nat Biotechnol 31, 530–532 (2013). https://doi.org/10.1038/nbt.2595

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