Abstract
EXPRESSION of Ets2, a proto-oncogene1 and transcription factor2–5, occurs in a variety of cell types6. During murine development it is highly expressed in newly forming cartilage, including in the skull precursor cells and vertebral primordia7. Ets2 is located on human chromosome 21 (ref. 8) and is overexpressed in Down's syndrome (trisomy 21)9. Here we generate transgenic mice to investigate the consequences of overexpression of Ets2. We find that mice with less than 2-foldEts2 overexpression in particular organs develop neurocranial, viscerocranial and cervical skeletal abnormalities. These abnormalities have similarities with the skeletal anomalies found in trisomy-16 mice and humans with Down's syndrome, in which the gene dosage of Ets2 is increased10,12. Our results indicate that Ets2 has a role in skeletal development and implicate the overexpression of Ets2 in the genesis of some skeletal abnormalities that occur in Down's syndrome.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Seth, A., Watson, D. K., Blair, D. G. & Papas, T. S. Proc. natn. Acad. Sci. U.S.A. 86, 7833–7837 (1989).
Wasylyk, B. et al. Nature 346, 191–193 (1990).
Ascione, R. et al. Int. J. Oncol. 1, 631–637 (1992).
Seth, A., Robinson, L., Thompson, D. M., Watson, D. K. & Papas, T. S. Oncogene 8, 1783–1790 (1993).
Thomas, R. S., Tymms, M. J., Seth, A., Shannon, M. F. & Kola, I. Oncogene 11, 2135–2143 (1995).
Kola, I. et al. Proc. natn. Acad. Sci. U.S.A. 90, 7588–7592 (1993).
Maroulakou, I. G., Papas, T. S. & Green, J. E. Oncogene 9, 1551–1165 (1994).
Chumakov, I. et al. Nature 359, 380–387 (1992).
Kola, I. et al. in Advances in Human Reproduction (eds Moeloek, F. A., Affandi, B. & Trounson, A. O.) 309–320 (Casterton-Parthenon, New York, 1995).
Korenberg, J. R. in The Morphogenesis of Down Syndrome (ed. Epstein. C. J.) 43–52 (Wiley-Liss, New York, 1991).
Reeves, R. H. et al. Molec. Brain Res. 2, 215–221 (1987).
Kaufman, M. H. in The Atlas of Mouse Development 495–507 (Academic, London, 1990).
Davisson, M. T. et al. Cytogenet. Cell Genet. 55, 434–456 (1990).
Epstein, L. B., Cox, D. R. & Epstein, C. J. Ann. NY Acad. Sci. 350, 171–173 (1980).
Caffey, J. in Paediatric X-Ray Diagnosis Vol. 1, 7th edn 155–157 (Year Book Medical, Chicago, 1978).
Grausz, H., Richtsmeier, J. T. & Oster-Granite, M. L. in Morphogenesis of Down Syndrome (ed. Epstein, C. J.) 169–188 (Wiley-Liss, New York, 1991).
Patterson, D. H. Sci. Am. 257, 42–49 (1987).
Avraham, K. B., Schickler, M., Sapoznikov, D., Yarom, R. & Groner, Y. Cell 54, 823–829 (1989).
Reeves, R. H. et al. Nature Genet. 111, 177–184 (1985).
Iannello, R. C., Young, J., Sumarsono, S., Tymms, M. J. & Kola, I. Reprod. Fertil. Dev. 6, 599–604 (1994).
Hart, A., Corrick, C. M., Tymms, M. T., Hertzog, P. J. & Kola, I. Oncogene 10, 1423–1430 (1995).
Tymms, M. J. in Methods in Molecular Biology—In Vitro Transcription and Translation Protocols Vol. 37 (ed. Tymms, M. J.) 31–46 (Humana, Totowa, New Jersey, 1995).
Bancroft, J. D. & Cook, H. C. Manual of Histological Techniques (Churchill Livingstone, London, 1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Heru Sumarsono, S., Wilson, T., Tymms, M. et al. Down's syndrome-like skeletal abnormalities in Ets2 transgenic mice. Nature 379, 534–537 (1996). https://doi.org/10.1038/379534a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/379534a0
This article is cited by
-
Migration deficits of the neural crest caused by CXADR triplication in a human Down syndrome stem cell model
Cell Death & Disease (2022)
-
Cyclin-dependent kinases and rare developmental disorders
Orphanet Journal of Rare Diseases (2020)
-
Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm
Clinical Epigenetics (2019)
-
Transcriptional dynamics of a conserved gene expression network associated with craniofacial divergence in Arctic charr
EvoDevo (2014)
-
Identification of Chiari Type I Malformation subtypes using whole genome expression profiles and cranial base morphometrics
BMC Medical Genomics (2014)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.