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Targetted correction of a mutant HPRT gene in mouse embryonic stem cells

Nature volume 330, pages 576–578 (1987)Cite this article

Abstract

Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells1 that can still enter the germline after genetic manipulation in culture2,3 and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DNA can be used in culture to modify specifically the target locus4. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse5. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways.

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References

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Author notes

  1. Oliver Smithies: To whom correspondence should be addressed.

Authors and Affiliations

  1. Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin, 53706, USA

    Thomas Doetschman, Ronald G. Gregg, Nobuyo Maeda & Oliver Smithies

  2. Department of Pathology, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK

    Martin L. Hooper

  3. Department of Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, UK

    David W. Melton & Simon Thompson

Authors
  1. Thomas Doetschman
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  2. Ronald G. Gregg
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  3. Nobuyo Maeda
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  4. Martin L. Hooper
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  5. David W. Melton
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  6. Simon Thompson
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  7. Oliver Smithies
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Doetschman, T., Gregg, R., Maeda, N. et al. Targetted correction of a mutant HPRT gene in mouse embryonic stem cells. Nature 330, 576–578 (1987). https://doi.org/10.1038/330576a0

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