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Down's syndrome-like skeletal abnormalities in Ets2 transgenic mice

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.

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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

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