Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Genomic imprinting of Mash2, a mouse gene required for trophoblast development

Abstract

The mouse gene Mash2 encodes a transcription factor required for development of trophoblast progenitors. Mash2− homozygous mutant embryos die at 10 days post–coitum from placental failure. Here we show that Mash2 is genomically imprinted. First, Mash2+/− embryos inheriting a wild–type allele from their father die at the same stage as −/− embryos, with a similar placental phenotype. Second, the Mash2 paternal allele is initially expressed by groups of trophoblast cells at 6.5 and 7.5 days post–coitum, but appears almost completely repressed by 8.5 days post–coitum. Finally, we have genetically and physically mapped Mash2 to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin–2, insulin–like growth factor–2 and H19.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Surani, M.A.H., Barton, S.C. & Morris, M.L. Nuclear transplantation in the mouse: Heritable differences between parental genomes after activation of the embryonic genome. Cell 45, 127–136 (1986).

    Article  CAS  PubMed  Google Scholar 

  4. Barton, S.C., Adams, C.A., Morris, M.L., Surani, M.A.H. Development of gynogenetic and parthenogenetic Inner cell mass and trophectoderm tissues In reconstituted blastocysts in the mouse. J. Embryol. exp. Morphol. 90, 267–285 (1985).

    CAS  PubMed  Google Scholar 

  5. Mann, J.R., Lovell-Badge, R.H. Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm. Nature 310, 66–67 (1984).

    Article  CAS  PubMed  Google Scholar 

  6. Surani, M.A. et al. Genome Imprinting and development In the mouse. Development Suppl., 89–98 (1990).

  7. Cattanach, B.M. & Kirk, M. Differential activity of maternally and paternally derived chromosome regions In mice. Nature 315, 496–498 (1985).

    Article  CAS  PubMed  Google Scholar 

  8. Cattanach, B.M. & Beechey, C.V. Autosomal and X-chromosome Imprinting. Development Suppl., 63–72 (1990).

  9. Beechey, C.V. & Cattanach, B.M. Genetic imprinting map. Mouse Genome 92, 108–110 (1993).

    Google Scholar 

  10. Barlow, D.P. Imprinting: a gamete's point of view. Trends Genet. 10, 194–199 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Efstratiadis, A. Imprinting of autosomal mammalian genes. Curr Opin. Genet. Dev. 4, 265–280 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Bartolomel, M.S., Zemel, S. & Tilghman, S.M. Imprinting of the mouse H19 gene. Nature 351, 153–155 (1991).

    Article  Google Scholar 

  13. DeChiara, T.M., Robertson, E.J. & Efstratiadis, A. Imprinting of the mouse Insulin-like growth factor II gene. Cell 64, 849–859 (1991).

    Article  CAS  PubMed  Google Scholar 

  14. Zemel, S., Bartolomel, M.S. & Tilghman, S.M. Physical linkage of two mammalian Imprinted genes, H19 and Insulin-like growth factor 2. Nature Genet. 2, 61–65 (1992).

    Article  CAS  PubMed  Google Scholar 

  15. Giddings, S.J., King, C.D., Harman, K.W., Flood, J.F. & Camaghi, L.R. Allele specific inactivation of Insulin 1 and 2, in the mouse yolk sac, indicates imprinting. Nature Genet. 6, 310–313 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Leff, S.E. et al. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nature Genet. 2, 259–264 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Searle, A.G. & Beechey, C.V. Imprinting phenomena on mouse chromosome 7. Genet. Res. 56, 237–244 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Ferguson-Smith, A.C., Cattanach, B.M., Barton, S.C., Beechey, C.V. & Surani, M.A. Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 351, 667–670 (1991).

    Article  CAS  PubMed  Google Scholar 

  19. Beechey, C.V. Further localization of the distal chromosome 7 imprinting region. Mouse Genome 91, 310–311 (1993).

    Google Scholar 

  20. Beechey, C.V. Genetic mapping studies of the distal chromosome 7 imprinting region. Mouse Genome 91, 857 (1993).

    Google Scholar 

  21. Mclaughlin, K.J., Szabo, P. & Mann, J.R. Mouse embryos with paternal duplication of distal chromosome 7 are lethal at midgestatlon and possess aberrant expression levels of Igf2 and H19. Genes Dev. (in the press).

  22. Barton, S.C., Surani, M.A. & Norris, M.L. Role of paternal and maternal genomes in mouse development. Nature 311, 374–376 (1984).

    Article  CAS  PubMed  Google Scholar 

  23. Hall, J.G. Genomic imprinting: review of relevance to human diseases. Am. J. hum. Genet 46, 857–873 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Johnson, J.E., Blrren, S.J., Anderson, D.J. Tworathomologues of Drosophila achaete-scute specifically expressed in neuronal precursors. Nature 346, 868–861 (1990).

    Article  Google Scholar 

  25. Johnson, J.E., Birren, S.J., Saito, T. & Anderson, D.J. DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer. Proc. natn. Acad. Sci. U.S.A. 89, 3596–3600 (1992).

    Article  CAS  Google Scholar 

  26. Guillemot, F. & Joyner, A.L. Dynamic expression of the murine achaete-scute homolog (MASH)-1 in the developing nervous system. Mech. Dev. 42, 171–185 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Guillemot, F., Nagy, A., Auerbach, A., Rossant, J. & Joyner, A.L. Essential role of Mash2 in extraembryonic development. Nature 371, 333–336 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Lescisin, K.R., Varmuza, S. & Rossant, J. Isolation and characterization of a novel trophoblast-specific cDNA in the mouse. Genes. Dev. 2, 1639–1646 (1989).

    Article  Google Scholar 

  29. Copeland, N.G. & Jenkins, M.A. Development and applications of a molecular genetic linkage map of the mouse genome. Trends Genet. 7, 113–118 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. Kitsberg, D. et al. Allele-specific replication timing of Imprinted gene regions. Nature 364, 459–463 (1993).

    Article  CAS  PubMed  Google Scholar 

  31. Bartolomel, M.S. & Tllghman, S.M. Imprinting of mouse chromosome 7. Seminars Dev. Biol. 3, 107–117 (1992).

    Google Scholar 

  32. Bartolomel, M.S., Webber, A.L., Brunkow, M.E. and Tilghman, S.M. Epigenetic mechanisms underlaying the imprinting of the mouse H19 gene. Genes Dev. 7, 1663–1673 (1993).

    Article  Google Scholar 

  33. Ferguson-Smith, A.C., Sasaki, H., Cattanach, B.M. & Surani, M.A. Parental-origin-specific modification of the mouse H19 gene. Nature 362, 751–755 (1993).

    Article  CAS  PubMed  Google Scholar 

  34. Brandels, M. et al. The ontogeny of allele-specific methylation associated with Imprinted genes In the mouse. EMBO J. 12, 3669–3677 (1993).

    Article  Google Scholar 

  35. Lee, J.E., Pintar, J. & Efstratiadis, A. Pattern of the Insulin-like growth factor II gene expression during early mouse embryogenesis. Development 110, 151–159 (1990).

    CAS  PubMed  Google Scholar 

  36. Polrier, F. et al. The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of Implantation in the developing embryo. Development 113, 1105–1114 (1991).

    Google Scholar 

  37. Martinez, C. & Modolell, J. Cross-regulatory interactions between the proneural achaete and scute genes of Drosophila. Science 251, 485–487 (1991).

    Article  Google Scholar 

  38. Nagy, A., Paldl, A., Dezso, L., Varg, L. & Magyar, A. Prenatal fate of parthenogenetic cells in mouse aggregation chimeras. Development 101, 67–71 (1987).

    CAS  PubMed  Google Scholar 

  39. Clarke, H.J., Varmuza, S., Prideaux, V.R. & Rossant, J. The developmental potential of parthenogenetically derived cells in chimeric mouse embryos: implications for the action of imprinting genes. Development 104, 175–182 (1988).

    CAS  PubMed  Google Scholar 

  40. Thomson, J.A. & Softer, D. The developmental fate of androgenetic, parthenogenetic, and gynogenetic cells in chimeric gastrulating mouse embryos. Genes Dev. 2, 1344–1351 (1988).

    Article  CAS  PubMed  Google Scholar 

  41. Mann, J.R., Gadl, I., Harbison, M.L., Abbondanzo, S.J. & Stewart, C.L. Androgenetic mouse embryonic stem cells are pluripotent and cause skeletal defects In chimeras: implications for genetic imprinting. Cell 62, 251–260 (1990).

    Article  CAS  PubMed  Google Scholar 

  42. Solter, D. Differential imprinting and expression of maternal and paternal genomes. A. Rev. Genet. 22, 127–146 (1988).

    Article  CAS  Google Scholar 

  43. Ghysen, A., Dambly-Chaudiere, C., Jan, L.Y. & Jan, Y.-N. Cell interactions and gene interactions in peripheral neurogenesis. Genes Dev. 7, 723–733 (1993).

    Article  CAS  PubMed  Google Scholar 

  44. Cline, T.W. The Drosophila sex determination signal: How do files count to two. Trends Genet. 9, 385–390 (1993).

    Article  CAS  PubMed  Google Scholar 

  45. Moens, C.B., Stanton, B.R., Parada, L.F. & Rossant, J. Defects in heart and lung development in compound heterozygotes for two different targeted mutations at the N-myc locus. Development 119, 485–499 (1993).

    CAS  PubMed  Google Scholar 

  46. Jenkins, N.A., Copeland, N.G., Taylor, B.A. & Lee, B.K. Organization, distribution, and stability of endogenous ecotropic murine leukemia virus DMA sequences in chromosomes of Mus musculus. J. Virol. 43, 26–36 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Avraham, K.B. et al. Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes. Genomics 21, 656–658 (1994).

    Article  CAS  PubMed  Google Scholar 

  48. Foroni, L. et al. The rhombotin gene family encode related LIM-domaln proteins whose differing expression suggests multiple roles in mouse development. J. molec. Biol. 226, 747–761 (1992).

    Article  CAS  PubMed  Google Scholar 

  49. Green, E.L. Linkage, recombination and mapping. in Genetics and Probability in Animal Breeding Experiments. 77–113 (Oxford University Press, New York, 1981).

    Chapter  Google Scholar 

  50. Chu, G., Volrath, D. & David, R.W. Separation of large DMA molecules by contour-clamped homogenous electric fields. Science 234, 1582–1585 (1986).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guillemot, F., Caspary, T., Tilghman, S. et al. Genomic imprinting of Mash2, a mouse gene required for trophoblast development. Nat Genet 9, 235–242 (1995). https://doi.org/10.1038/ng0395-235

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0395-235

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing