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Science 23 September 2005:
Vol. 309. no. 5743, pp. 2033 - 2037
DOI: 10.1126/science.1114535
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Research Articles

An Aneuploid Mouse Strain Carrying Human Chromosome 21 with Down Syndrome Phenotypes

Aideen O'Doherty,1,3 Sandra Ruf,1,3 Claire Mulligan,4 Victoria Hildreth,5 Mick L. Errington,3 Sam Cooke,3 Abdul Sesay,3 Sonie Modino,6 Lesley Vanes,3 Diana Hernandez,1,3 Jacqueline M. Linehan,1,2 Paul T. Sharpe,6 Sebastian Brandner,1 Timothy V. P. Bliss,3 Deborah J. Henderson,5 Dean Nizetic,4 Victor L. J. Tybulewicz,3* Elizabeth M. C. Fisher1*

Aneuploidies are common chromosomal defects that result in growth and developmental deficits and high levels of lethality in humans. To gain insight into the biology of aneuploidies, we manipulated mouse embryonic stem cells and generated a trans-species aneuploid mouse line that stably transmits a freely segregating, almost complete human chromosome 21 (Hsa21). This "transchromosomic" mouse line, Tc1, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, heart development, and mandible size that relate to human DS. Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies.

1 Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
2 Medical Research Council Prion Unit, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
3 National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
4 Centre for Haematology, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine, 4 Newark Street, London E1 2AT, UK.
5 Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
6 Department of Craniofacial Development, Kings College London, Guy's Hospital, London SE1 9RT, UK.

* To whom correspondence should be addressed. E-mail: vtybule{at}nimr.mrc.ac.uk (V.L.J.T); e.fisher{at}prion.ucl.ac.uk (E.M.C.F.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)