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

De Cegli, Rossella
Romito, Antonio
Iacobacci, Simona
Mao, Lei
Lauria, Mario
Fedele, Anthony O.
Klose, Joachim
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Published in GenomeBiology.com. 2010, vol. 11, no. 6, R64
Abstract BACKGROUND: Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21. RESULTS: 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. CONCLUSIONS: 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.
Keywords AnimalsCell LineChromosomes, Human, Pair 21/*geneticsCore Binding Factor Alpha 2 Subunit/genetics/metabolismEmbryonic Stem Cells/*cytology/*metabolismGene Dosage/geneticsGene Expression Profiling*Gene Expression RegulationHumansMiceMice, TransgenicPolymerase Chain ReactionProteome/metabolismRecombination, GeneticReproducibility of ResultsTime Factors*Tissue BanksTranscription, Genetic
PMID: 20569505
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Research group Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
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DE CEGLI, Rossella et al. A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes. In: GenomeBiology.com, 2010, vol. 11, n° 6, p. R64. doi: 10.1186/gb-2010-11-6-r64 https://archive-ouverte.unige.ch/unige:20619

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Deposited on : 2012-05-22

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