UK researchers have produced a mouse with extra human genetic material that mimics Down syndrome much more accurately than previous mouse ‘models’ for this condition. The scientists, based at the UK’s National Institute for Medical Research and the Institute of Neurology at University College London, hope the mouse will shed light on the many health problems that can affect people born with the condition.

Down syndrome – which affects around one in every 750 births – is caused by the presence of three copies of chromosome 21 (the smallest ‘bundle’ of human genetic material), rather than the usual two. The new mouse strain has an extra copy of almost all of human chromosome 21, say the scientists, who published their findings in the journal Science. Previous mouse models for Down syndrome had extra copies of the mouse genes that corresponded to those found on human chromosome 21. However, since these genes are spread out over three different mouse chromosomes, none of the existing models of Down syndrome had a ‘complete set’ of the extra genes involved.

Co-author Elizabeth Fisher said that people with Down syndrome have particular susceptibilities for diseases such as leukaemias and autoimmune disorders. ‘We believe this technology will help us work out why this is, and what to do about it’, she added. The team created the new strain of mouse by exposing mouse embryonic stem cells (ES cells) to human chromosomes, and selecting those that absorbed chromosome 21. They then injected the ES cells into three-day-old mouse embryos, which they reimplanted into female mice. After many attempts, and further modifications, the scientists managed to create a new strain of mouse, dubbed ‘Tc1’, that has about 92 per cent of human chromosome 21 permanently added to its genetic material.

The mice have many of the features of Down syndrome, including problems with learning and memory similar to those that affect Down syndrome patients. Unlike previous mouse models, the animals also have heart defects, which affect around 40 per cent of people born with the condition. Victor Tybulewicz, who co-authored the study, says it should now be possible to ‘knock out’ individual chromosome 21 genes in the mice, to investigate their role in Down syndrome. ‘This should illuminate which genes lead to heart defects, the higher risk of leukaemia and early onset Alzheimer’s’, he said.

Scientists welcomed the news, describing it as ‘a technical tour de force’, and as a development that will have ‘a huge impact on Down syndrome research’. US geneticist Julie Kornberg says the Tc1 mouse is a ‘superb model’, and is superior to other mouse models of Down syndrome because it has many more of the genes involved, as well as the human DNA that controls those genes. But David King, of the UK pressure group Human Genetics Alert, expressed fears that the breakthrough represented ‘genetic engineering taken to another level’. He told the Guardian newspaper: ‘If more chromosomes are put in, are we going to have to start giving these things pseudo human rights?’ Dr Fisher countered by saying ‘we’re not trying to humanise mice, we’re trying to tease out the genetics of a very complex disorder’.

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