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Generation of rat mutants using a coat color-tagged Sleeping Beauty transposon system

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Abstract

A significant barrier to exploiting the full potential of the rat as a biomedical model is the lack of tools to easily modify its germline. Here we show that a tyrosinase-tagged Sleeping Beauty transposon can be used as a simple, efficient method to generate rat mutants in vivo. By making two lines of transgenic rats, one carrying the transposon and another expressing the transposase in germ cells, we are able to obtain bigenic males in which transposition occurs in the germ cells. We show that transposition leads to the appearance of new coat colors in the offspring. Using such bigenic males, we obtained an average of 1.2 transpositions per gamete and identified 19 intragenic integration events among 96 transposition sites that were sequenced. In addition, gene trapping was confirmed and rats with evidence for transposon-induced dominant ocular anomalies were identified. These data suggest that the modified Sleeping Beauty transposon represents a powerful new tool for producing molecularly defined mutagenesis in the rat.

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Acknowledgments

The authors thank Carolyn Castile and Helen Martinez for excellent technical support. This work was funded by NIH grant R21RR021947 to CEB.

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Author notes

  1. Christophe Poirier

    Present address: Department of Pediatrics, University of Chicago, Chicago, IL, 60637, USA

  2. Deborah C. Petit

    Present address: Department of Veterinary Medicine and Surgery, University of Texas, M.D. Anderson Cancer Center, Houston, TX, 77030, USA

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Baisong Lu, Christophe Poirier, Deborah C. Petit & Colin E. Bishop

  2. Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, 27157, USA

    Baisong Lu & Colin E. Bishop

  3. Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA

    Aron M. Geurts

  4. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA

    Wilbur Harrison & Paul A. Overbeek

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  1. Baisong Lu
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Correspondence to Colin E. Bishop.

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Lu, B., Geurts, A.M., Poirier, C. et al. Generation of rat mutants using a coat color-tagged Sleeping Beauty transposon system. Mamm Genome 18, 338–346 (2007). https://doi.org/10.1007/s00335-007-9025-5

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  • DOI: https://doi.org/10.1007/s00335-007-9025-5

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