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A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes

Rossella De Cegli1, Antonio Romito12, Simona Iacobacci1, Lei Mao3, Mario Lauria1, Anthony O Fedele14, Joachim Klose3, Christelle Borel5, Patrick Descombes6, Stylianos E Antonarakis5, Diego di Bernardo1, Sandro Banfi1, Andrea Ballabio1 and Gilda Cobellis17*

Author Affiliations

1 Telethon Institute of Genetics and Medicine, Via P. Castellino 111, Napoli, 80131, Italy

2 Current address: Université Paris Diderot - Paris 7, Paris Cedex 13, Paris, 75205, France

3 Institut für Humangenetik Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, D-13353, Germany

4 Current address: Lysosomal Diseases Research Unit, SA Pathology, 72 King William Road, North Adelaide, South Australia, 5006, Australia

5 Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel-Servet, Geneva, CH-1211, Switzerland

6 Genomics Platform, University of Geneva Medical School, 1 rue Michel-Servet, Geneva, CH-1211, Switzerland

7 Current address: Dipartimento di Patologia Generale, Seconda Universita' di Napoli, Via De Crecchio 7, Napoli, 80100, Italy

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Genome Biology 2010, 11:R64  doi:10.1186/gb-2010-11-6-r64

Published: 22 June 2010



Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.


To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which can be overexpressed in an inducible manner. Each clone was transcriptionally profiled in inducing versus non-inducing conditions. Analysis of the transcriptional response yielded results that were consistent with the perturbed gene's known function. Comparison between mouse ES cells containing the whole human chromosome 21 (trisomic mouse ES cells) and mouse ES cells overexpressing single human chromosome 21 genes allowed us to evaluate the contribution of single genes to the trisomic mouse ES cell transcriptome. In addition, for the clones overexpressing the Runx1 gene, we compared the transcriptome changes with the corresponding protein changes by mass spectroscopy analysis.


We determined that only a subset of genes produces a strong transcriptional response when overexpressed in mouse ES cells and that this effect can be predicted taking into account the basal gene expression level and the protein secondary structure. We showed that the human chromosome 21-mouse ES cell bank is an important resource, which may be instrumental towards a better understanding of Down syndrome and other human aneuploidy disorders.