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

Nature. 1996 Feb 8;379(6565):534-7. doi: 10.1038/379534a0.


Expression of Ets2, a proto-oncogene and transcription factor, occurs in a variety of cell types. During murine development it is highly expressed in newly forming cartilage, including in the skull precursor cells and vertebral primordia. Ets2 is located on human chromosome 21 (ref. 8) and is overexpressed in Down's syndrome (trisomy 21). Here we generate transgenic mice to investigate the consequences of overexpression of Ets2. We find that mice with less than 2-fold Ets2 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 increased. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Animals
  • Base Sequence
  • Bone and Bones / abnormalities*
  • Bone and Bones / embryology
  • DNA Primers
  • DNA-Binding Proteins*
  • Down Syndrome / genetics*
  • Down Syndrome / pathology
  • Fetus / abnormalities
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Repressor Proteins*
  • Skull / abnormalities
  • Spine / abnormalities
  • Trans-Activators*
  • Transcription Factors*
  • Trisomy / pathology


  • DNA Primers
  • DNA-Binding Proteins
  • ERF protein, human
  • ETS2 protein, human
  • Ets2 protein, mouse
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors