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Male and female mice derived from the same embryonic stem cell clone by tetraploid embryo complementation - Nature Biotechnology

  • ️Jaenisch, Rudolf
  • ️Wed May 01 2002

Abstract

We have devised a general strategy for producing female mice from 39,X0 embryonic stem (ES) cells derived from male cell lines carrying a targeted mutation of interest. We show that the Y chromosome is lost in 2% of subclones from 40,XY ES cell lines, making the identification of targeted 39,X0 subclones a routine procedure. After gene targeting, male and female mice carrying the mutation can be generated by tetraploid embryo complementation from the 40,XY ES cell line and its 39,X0 derivatives. A single intercross then produces homozygous mutant offspring. Because this strategy avoids outcrossing and therefore segregation of mutant alleles introduced into the ES cells, the time and expense required for production of experimental mutant animals from a targeted ES cell clone are substantially reduced. Our data also indicate that ES cells have inherently unstable karyotypes, but this instability does not interfere with production of adult ES cell–tetraploid mice.

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Acknowledgements

We would like to thank D. Page, W.M. Rideout, C. Beard, K. Hochedlinger, A. Bortvin, M. Rios, and D. Menke for helpful discussions. This work was supported in part by NIH grants 5-R35-CA44339 and RO1-CA84198 to R. Jaenisch. I. Jentsch received a stipend from TILL I.D., Gräfeling, Germany.

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, 02142, MA, USA

    Kevin Eggan, Jennifer Erwin, Janet Loring, Laurie Jackson-Grusby & Rudolf Jaenisch

  2. Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, 02142, MA, USA

    Kevin Eggan, Jennifer Erwin & Rudolf Jaenisch

  3. Artemis Pharmaceuticals GmbH, Neurather Ring 1, Cologne, D-51063, Germany

    Anja Rode, Caroline Samuel, Thomas Hennek, Hartmut Tintrup, Branko Zevnik & Ralf Kuehn

  4. Institute of Human Genetics, Technical University, Munich, Germany

    Isabell Jentsch & Michael R. Speicher

  5. Institute of Human Genetics, GSF National Research Center, Munich, Germany

    Isabell Jentsch & Michael R. Speicher

Authors

  1. Kevin Eggan

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  2. Anja Rode

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  3. Isabell Jentsch

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  4. Caroline Samuel

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  5. Thomas Hennek

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  6. Hartmut Tintrup

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  7. Branko Zevnik

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  8. Jennifer Erwin

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  9. Janet Loring

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  10. Laurie Jackson-Grusby

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  11. Michael R. Speicher

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  12. Ralf Kuehn

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  13. Rudolf Jaenisch

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Corresponding author

Correspondence to Rudolf Jaenisch.

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Competing interests

A.R., C.S., T.H., H.T., B.Z., and R.K. are employed by Artemis Pharmaceuticals, Cologne, and will use some of the results reported here for their ongoing commercial interests. The remaining authors are all at academic institutions that are supported by public funds and have no competing interests in this research.

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Eggan, K., Rode, A., Jentsch, I. et al. Male and female mice derived from the same embryonic stem cell clone by tetraploid embryo complementation. Nat Biotechnol 20, 455–459 (2002). https://doi.org/10.1038/nbt0502-455

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  • Received: 06 December 2001

  • Accepted: 13 February 2002

  • Issue Date: 01 May 2002

  • DOI: https://doi.org/10.1038/nbt0502-455