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Birth of parthenogenetic mice that can develop to adulthood

Abstract

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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Acknowledgements

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). https://doi.org/10.1038/nature02402

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