18 May 2005
Down's Syndrome is the most common chromosomal abnormality that affects live born babies; it is caused by trisomy of human chromosome 21. Usually this trisomy is complete (the presence of a complete additional copy of chromosome 21) but in some cases only partial trisomy with respect to this chromosome is observed. Down's Syndrome results in mental retardation in association with certain characteristic facial and physical features, as well as other medical conditions affecting the heart and gastrointestinal tract. These clinical features of the syndrome are presumed to be the result of abnormally increased levels of gene expression from the additional copy of chromosome 21; previous research has suggested that a certain subset of genes are likely to be key in causing disease. Together these genes are referred to as the Down Syndrome Critical Region (DSCR) of chromosome 21.
A new paper in Science reports that this region does not account for the craniofacial abnormalities associated with Down syndrome [Olson LE et al. (2004) Science 306, 687-690]. Researchers from Johns Hopkins in the US created mouse models for DS by engineering mice that were trisomic for the murine equivalent of the DSCR only, with a view to producing improved disease models. Mouse models for Down syndrome exist, but have been complicated to develop; most of the orthologous murine genes for those found on human chromosome 21 are present on the mouse chromosome 16, but mice with trisomy 16 are not viable. It was therefore necessary to develop mice with segmental trisomy for orthologues of human chromosome 21 genes; these mice are not perfect models of DS but show significant phenotypic similarities to the human syndrome, including craniofacial, neurological and behavioural changes.
The team created genetically engineered mice with either a duplication or deletion of a section of mouse chromosome 16 containing the 33 genes equivalent to those present in the human DSCR