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Generating somatic mosaicism with a Cre recombinase–microsatellite sequence transgene

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Abstract

Strategies for altering constitutional or somatic genotype in mice are well established, but approaches to generate mosaic genotypes in mouse tissues are limited. We showed that a functionally inactive Cre recombinase transgene with a long mononucleotide tract altering the reading frame was stochastically activated in the mouse intestinal tract. We demonstrated the utility of this approach by inducing colonic polyposis after Cre-mediated bi-allelic inactivation of the Apc gene.

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Figure 1: CDX2P9.5-G22Cre transgenic mice and somatic activation of Cre function.
Figure 2: Polyposis in cecum and proximal colon in CDX2P9.5-G22Cre;Apcflox/flox mice.

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Acknowledgements

We thank T. Saunders and the University of Michigan Transgenic Core for outstanding support of the transgenic studies, the University of Michigan Microscopy and Image Analysis Laboratory for assistance with microscopy, S. Camper (University of Michigan) for providing R26R mice and the caggB plasmid, S. Tarle for technical assistance, and K.R. Cho for helpful discussions. This work was supported by US National Institutes of Health grants CA082223, CA085463 and GM067840.

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Author notes

  1. Aytekin Akyol & Takao Hinoi

    Present address: Present addresses: Hacettepe University School of Medicine Department of Pathology, 06100 Shihhiye, Ankara, Turkey (A.A.) and Department of Surgery, Hiroshima University, 1-2-3 Kasumi, Minami-ku Hiroshima 734-8551, Japan (T.H.).,

Authors and Affiliations

  1. Department of Internal Medicine, University of Michigan Medical School, 109 Zina Pitcher, Ann Arbor, 48109, Michigan, USA

    Aytekin Akyol, Takao Hinoi, Ying Feng, Guido T Bommer, Thomas M Glaser & Eric R Fearon

  2. Department of Human Genetics, University of Michigan Medical School, 109 Zina Pitcher, Ann Arbor, 48109, Michigan, USA

    Thomas M Glaser & Eric R Fearon

  3. Department of Pathology, University of Michigan Medical School, 109 Zina Pitcher, Ann Arbor, 48109, Michigan, USA

    Eric R Fearon

  4. The Cancer Center, University of Michigan Medical School, 109 Zina Pitcher, Ann Arbor, 48109, Michigan, USA

    Eric R Fearon

Authors
  1. Aytekin Akyol
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  2. Takao Hinoi
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  3. Ying Feng
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  4. Guido T Bommer
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  5. Thomas M Glaser
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  6. Eric R Fearon
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Contributions

A.A., T.H., Y.F. and G.T.B. performed experiments. T.M.G. provided key reagents. E.R.F. supervised the work and wrote the manuscript.

Corresponding author

Correspondence to Eric R Fearon.

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Supplementary Figures 1–4, Supplementary Table 1, Supplementary Methods (PDF 655 kb)

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Akyol, A., Hinoi, T., Feng, Y. et al. Generating somatic mosaicism with a Cre recombinase–microsatellite sequence transgene. Nat Methods 5, 231–233 (2008). https://doi.org/10.1038/nmeth.1182

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  • DOI: https://doi.org/10.1038/nmeth.1182

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