Nature Genetics
9, 235 - 242 (1995)
doi:10.1038/ng0395-235
Genomic imprinting of Mash2, a mouse gene required for trophoblast developmentFrançois Guillemot1, 2, 7, Tamara Caspary3, Shirley M. Tilghman3, Neal G. Copeland4, Debra J. Gilbert4, Nancy A. Jenkins4, David J. Anderson5, Alexandra L. Joyner1, 6, 8, Janet Rossant1,6
& András Nagy1
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, M5G 1X5 Toronto, Canada
2Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-Université Louis Pasteur, C.U. de Strasbourg, 67404 Illkirch, France
3HHMI and Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA
4Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA
5HHMI, Division of Biology, California Institute of Technology, Pasadena, California 91106, USA
6Department of Molecular and Medical Genetics, University of Toronto, M5S 1A8 Toronto, Canada
7Present address: IGBMC, B.P.163, 67404 Illkirch Cédex, France
8Present address: New York University Medical Center, Skirball Institute of Biomolecular Medicine, New York, New York 10016, USA Correspondence should be addressed to F.G. 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.
REFERENCES
- McGrath, J. & Sorter, D. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179−183 (1984). | Article | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- Mann, J.R., Lovell-Badge, R.H. Inviability of parthenogenones is determined by pronuclei, not egg cytoplasm. Nature 310, 66−67 (1984). | PubMed | ISI | ChemPort |
- Surani, M.A. et al. Genome Imprinting and development In the mouse. Development Suppl., 89−98 (1990). | ChemPort |
- Cattanach, B.M. & Kirk, M. Differential activity of maternally and paternally derived chromosome regions In mice. Nature 315, 496−498 (1985). | PubMed | ISI | ChemPort |
- Cattanach, B.M. & Beechey, C.V. Autosomal and X-chromosome Imprinting. Development Suppl., 63−72 (1990). | PubMed | ChemPort |
- Beechey, C.V. & Cattanach, B.M. Genetic imprinting map. Mouse Genome 92, 108−110 (1993).
- Barlow, D.P. Imprinting: a gamete's point of view. Trends Genet. 10, 194−199 (1994). | Article | PubMed | ISI | ChemPort |
- Efstratiadis, A. Imprinting of autosomal mammalian genes. Curr Opin. Genet. Dev. 4, 265−280 (1994). | PubMed | ChemPort |
- Bartolomel, M.S., Zemel, S. & Tilghman, S.M. Imprinting of the mouse H19 gene. Nature 351, 153−155 (1991). | Article | PubMed | ISI | ChemPort |
- DeChiara, T.M., Robertson, E.J. & Efstratiadis, A. Imprinting of the mouse Insulin-like growth factor II gene. Cell 64, 849−859 (1991). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- Searle, A.G. & Beechey, C.V. Imprinting phenomena on mouse chromosome 7. Genet. Res. 56, 237−244 (1990). | PubMed | ISI | ChemPort |
- 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 | PubMed | ChemPort |
- Beechey, C.V. Further localization of the distal chromosome 7 imprinting region. Mouse Genome 91, 310−311 (1993).
- Beechey, C.V. Genetic mapping studies of the distal chromosome 7 imprinting region. Mouse Genome 91, 857 (1993).
- 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).
- Barton, S.C., Surani, M.A. & Norris, M.L. Role of paternal and maternal genomes in mouse development. Nature 311, 374−376 (1984). | PubMed | ISI | ChemPort |
- Hall, J.G. Genomic imprinting: review of relevance to human diseases. Am. J. hum. Genet 46, 857−873 (1990). | PubMed | ISI | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- 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). | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- Guillemot, F., Nagy, A., Auerbach, A., Rossant, J. & Joyner, A.L. Essential role of Mash2 in extraembryonic development. Nature 371, 333−336 (1994). | Article | PubMed | ISI | ChemPort |
- 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). | ISI |
- 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 | PubMed | ISI | ChemPort |
- Kitsberg, D. et al. Allele-specific replication timing of Imprinted gene regions. Nature 364, 459−463 (1993). | Article | PubMed | ISI | ChemPort |
- Bartolomel, M.S. & Tllghman, S.M. Imprinting of mouse chromosome 7. Seminars Dev. Biol. 3, 107−117 (1992).
- 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). | PubMed | ISI | ChemPort |
- 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 | PubMed | ChemPort |
- Brandels, M. et al. The ontogeny of allele-specific methylation associated with Imprinted genes In the mouse. EMBO J. 12, 3669−3677 (1993). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- Martinez, C. & Modolell, J. Cross-regulatory interactions between the proneural achaete and scute genes of Drosophila. Science 251, 485−487 (1991).
- Nagy, A., Paldl, A., Dezso, L., Varg, L. & Magyar, A. Prenatal fate of parthenogenetic cells in mouse aggregation chimeras. Development 101, 67−71 (1987). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- Solter, D. Differential imprinting and expression of maternal and paternal genomes. A. Rev. Genet. 22, 127−146 (1988). | Article | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- Cline, T.W. The Drosophila sex determination signal: How do files count to two. Trends Genet. 9, 385−390 (1993). | Article | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- Green, E.L. Linkage, recombination and mapping. in Genetics and Probability in Animal Breeding Experiments. 77−113 (Oxford University Press, New York, 1981).
- Chu, G., Volrath, D. & David, R.W. Separation of large DMA molecules by contour-clamped homogenous electric fields. Science 234, 1582−1585 (1986). | PubMed | ISI | ChemPort |
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