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An Aneuploid Mouse Strain Carrying Human Chromosome 21 with Down Syndrome Phenotypes
Aideen O'Doherty,1,3Sandra Ruf,1,3Claire Mulligan,4Victoria Hildreth,5Mick L. Errington,3Sam Cooke,3Abdul Sesay,3Sonie Modino,6Lesley Vanes,3Diana Hernandez,1,3Jacqueline M. Linehan,1,2Paul T. Sharpe,6Sebastian Brandner,1Timothy V. P. Bliss,3Deborah J. Henderson,5Dean Nizetic,4Victor L. J. Tybulewicz,3*Elizabeth M. C. Fisher1*
Aneuploidies are common chromosomal defects that result in growthand developmental deficits and high levels of lethality in humans.To gain insight into the biology of aneuploidies, we manipulatedmouse embryonic stem cells and generated a trans-species aneuploidmouse line that stably transmits a freely segregating, almostcomplete human chromosome 21 (Hsa21). This "transchromosomic"mouse line, Tc1, is a model of trisomy 21, which manifests asDown syndrome (DS) in humans, and has phenotypic alterationsin behavior, synaptic plasticity, cerebellar neuronal number,heart development, and mandible size that relate to human DS.Transchromosomic mouse lines such as Tc1 may represent usefulgenetic 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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