Male and female mice derived from the same embryonic stem cell clone by tetraploid embryo complementation - Nature Biotechnology
- ️Jaenisch, Rudolf
- ️Wed May 01 2002
- Article
- Published: 01 May 2002
- Anja Rode3,
- Isabell Jentsch4,5,
- Caroline Samuel3,
- Thomas Hennek3,
- Hartmut Tintrup3,
- Branko Zevnik3,
- Jennifer Erwin1,2,
- Janet Loring1,
- Laurie Jackson-Grusby1,
- Michael R. Speicher4,5,
- Ralf Kuehn3 &
- …
- Rudolf Jaenisch1,2
Nature Biotechnology volume 20, pages 455–459 (2002)Cite this article
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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
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
Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, 02142, MA, USA
Kevin Eggan, Jennifer Erwin & Rudolf Jaenisch
Artemis Pharmaceuticals GmbH, Neurather Ring 1, Cologne, D-51063, Germany
Anja Rode, Caroline Samuel, Thomas Hennek, Hartmut Tintrup, Branko Zevnik & Ralf Kuehn
Institute of Human Genetics, Technical University, Munich, Germany
Isabell Jentsch & Michael R. Speicher
Institute of Human Genetics, GSF National Research Center, Munich, Germany
Isabell Jentsch & Michael R. Speicher
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- Kevin Eggan
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- Anja Rode
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- Isabell Jentsch
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- Caroline Samuel
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- Thomas Hennek
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- Hartmut Tintrup
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- Branko Zevnik
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- Jennifer Erwin
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- Janet Loring
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- Laurie Jackson-Grusby
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- Michael R. Speicher
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- Ralf Kuehn
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- Rudolf Jaenisch
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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
Received: 06 December 2001
Accepted: 13 February 2002
Issue Date: 01 May 2002
DOI: https://doi.org/10.1038/nbt0502-455