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Birth of parthenogenetic mice that can develop to adulthood


Only mammals have relinquished parthenogenesis, a means of producing descendants solely from maternal germ cells. Mouse parthenogenetic embryos die by day 10 of gestation1,2,3,4. Bi-parental reproduction is necessary because of parent-specific epigenetic modification of the genome during gametogenesis5,6,7,8. This leads to unequal expression of imprinted genes from the maternal and paternal alleles9. However, there is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development. Here we show the development of a viable parthenogenetic mouse individual from a reconstructed oocyte containing two haploid sets of maternal genome, derived from non-growing and fully grown oocytes. This development was made possible by the appropriate expression of the Igf2 and H19 genes with other imprinted genes, using mutant mice with a 13-kilobase deletion in the H19 gene10 as non-growing oocytes donors. This full-term development is associated with a marked reduction in aberrantly expressed genes. The parthenote developed to adulthood with the ability to reproduce offspring. These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant.

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Figure 1: Parthenogenetic mice derived from ngH19Δ13/fgwt embryos.
Figure 2: Parthenogenetic fetuses at day 12.5 of gestation.
Figure 3: Graphical representations of the expression of the two sets of coordinate imprinted genes in parthenogentic fetuses.

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  1. Surani, M. A. H. & Barton, S. C. Development of gynogenetic eggs in the mouse: Implications for parthenogenetic embryos. Science 222, 1034–1036 (1983)

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Surani, M. A. H., Barton, S. C. & Norris, M. L. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308, 548–550 (1984)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Surani, M. A. et al. Genome imprinting and development in the mouse. Development (suppl.), 89–98 (1990)

  4. McGrath, J. & Solter, D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179–183 (1984)

    Article  CAS  PubMed  Google Scholar 

  5. Brannan, C. I. & Bartolomei, M. S. Mechanisms of genomic imprinting. Curr. Opin. Genet. Dev. 9, 164–170 (1999)

    Article  CAS  PubMed  Google Scholar 

  6. Tilghman, S. M. The sins of the fathers and mothers: Genomic imprinting in mammalian development. Cell 96, 185–193 (1999)

    Article  CAS  PubMed  Google Scholar 

  7. Mann, J. R. Imprinting in the germ line. Stem Cells 19, 287–294 (2001)

    Article  CAS  PubMed  Google Scholar 

  8. Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nature 3, 662–673 (2002)

    CAS  Google Scholar 

  9. Obata, Y. & Kono, T. Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth. J. Biol. Chem. 277, 5285–5289 (2002)

    Article  CAS  PubMed  Google Scholar 

  10. Leighton, P. A., Ingram, R. S., Eggenschwiler, J., Efstratiadis, A. & Tilghman, S. M. Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375, 34–39 (1995)

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Lucifero, D., Mertineit, C., Clarke, H. J., Bestor, T. H. & Trasler, J. M. Methylation dynamics of imprinted genes in mouse germ cells. Genomics 79, 530–538 (2002)

    Article  CAS  PubMed  Google Scholar 

  12. Kono, T., Obata, Y., Yoshimzu, T., Nakahara, T. & Carroll, J. Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse. Nature Genet. 13, 91–94 (1996)

    Article  CAS  PubMed  Google Scholar 

  13. Obata, Y. et al. Disruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes during embryogenesis. Development 125, 1553–1560 (1998)

    CAS  PubMed  Google Scholar 

  14. Feil, R., Walter, J., Allen, N. D. & Reik, W. Developmental control of allelic methylation in the imprinted mouse Igf2 and H19 genes. Development 120, 2933–2943 (1994)

    CAS  PubMed  Google Scholar 

  15. Thorvaldsen, J. L., Duran, K. L. & Bartolomei, M. S. Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev. 12, 3693–3702 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hark, A. T. et al. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405, 486–489 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Leighton, P. A., Saam, J. R., Ingram, R. S., Stewart, C. L. & Tilghman, S. M. An enhancer deletion affects both H19 and Igf2 expression. Genes Dev. 9, 2079–2089 (1995)

    Article  CAS  PubMed  Google Scholar 

  18. Ripoche, M. A., Kress, C., Poirier, F. & Dandolo, L. Deletion of the H19 transcription unit reveals the existence of a putative imprinting control element. Genes Dev. 11, 1596–1604 (1997)

    Article  CAS  PubMed  Google Scholar 

  19. Kono, T., Sotomaru, Y., Katsuzawa, Y. & Dandolo, L. Mouse parthenogenetic embryos with monoallelic H19 expression can develop to day 17.5 of gestation. Dev. Biol. 243, 294–300 (2002)

    Article  CAS  PubMed  Google Scholar 

  20. Wang, Z. Q., Fung, M. R., Barlow, D. P. & Wagner, E. F. Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. Nature 372, 464–467 (1994)

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Theiler, K. The House Mouse: Atlas of Embryonic Development 122–128 (Springer, Berlin, 1989)

    Google Scholar 

  22. Eisen, M. B., Spellman, P. T., Brown, P. O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA 95, 14863–14868 (1998)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schmidt, J. V., Matteson, P. G., Jones, B. K., Guan, X. J. & Tilghman, S. M. The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Genes Dev. 14, 1997–2002 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Kobayashi, S. et al. Mouse Peg9/Dlk1 and human PEG9/DLK1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes: mouse Meg3/Gtl2 and human MEG3. Genes Cells 5, 1029–1037 (2000)

    Article  CAS  PubMed  Google Scholar 

  25. Lin, S. P. et al. Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nature Genet. 35, 97–102 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. Georgiades, P., Watkins, M., Surani, M. A. & Ferguson-Smith, A. C. Parental origin-specific developmental defects in mice with uniparental disomy for chromosome 12. Development 127, 4719–4728 (2000)

    CAS  PubMed  Google Scholar 

  27. Georgiades, P., Watkins, M., Burton, G. J. & Ferguson-Smith, A. C. Roles for genomic imprinting and the zygotic genome in placental development. Proc. Natl Acad. Sci. USA 98, 4522–4527 (2001)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moore, T. & Haig, D. Genomic imprinting in mamalian development: a parental tug-of -war. Trends Genet. 7, 45–49 (1991)

    Article  CAS  PubMed  Google Scholar 

  29. Reik, W. & Walter, J. Genomic imprinting: parental influence on the genome. Nature Rev. Genet. 2, 21–32 (2001)

    Article  CAS  PubMed  Google Scholar 

  30. Murphy, S. K. & Jirtle, R. L. Imprinting evolution and the price of silence. BioEssays 25, 577–588 (2003)

    Article  CAS  PubMed  Google Scholar 

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We thank A. Surani, Wellcome CRC Institute, J. Carroll, University College London and T. Moore, University College Cork, Ireland, for critical reading and discussions; O.-Y. Kwon, MacroGen, for microarray analysis; and T. Kumagai for technical assistance. This work was supported by grants from the Bio-oriented Technology Research Advancement Institution (BRAIN), Japan, and The Ministry of Education, Science, Culture and Sports of Japan.

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Correspondence to Tomohiro Kono.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

Expression profile comparisons by oligonucleotide mouse 11K microarray analysis. (JPG 108 kb)

Supplementary Figure 2

Graphical representation of ontology comparison. (JPG 346 kb)

Supplementary Figure 3

Histograms of a number of differentially expressed genes. (JPG 151 kb)

Supplementary Figure 4

Histograms of a number of differentially expressed genes. (JPG 220 kb)

Supplementary Figure Legends (DOC 19 kb)

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Kono, T., Obata, Y., Wu, Q. et al. Birth of parthenogenetic mice that can develop to adulthood. Nature 428, 860–864 (2004).

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