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Modifications du transcriptome au cours du développement postnatal du cervelet dans un modèle murin de Trisomie 21

Abstract : Down syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. Recent studies have demonstrated increased transcript levels for the three-copy genes with some dosage compensation or amplification for a subset of them but the impact of this gene dosage effect on the whole transcriptome is still debated. We thus designed a large scale gene expression study in the Ts1Cje Down syndrome mouse model in which we could measure the effects of trisomy 21 in the cerebellum that is affected in Down syndrome and where we could quantify the defects during postnatal development in order to correlate gene expression changes to the phenotype observed. Statistical analysis of microarray data revealed a major gene dosage effect : for the threecopy genes as well as for a 2Mb segment that we show for the first time as being deleted in the Ts1Cje mice using comparative genomic hybridization. This gene dosage effect impacts moderately on the expression of euploid genes (2.4 to 7.5% differentially expressed). Only 13 genes were significantly dysregulated in Ts1Cje mice across development and among them 6 are three-copy genes. Moreover, the decrease in granule cell proliferation that we demonstrated in newborn Ts1Cje cerebellum was correlated with a major gene dosage effect on the transcriptome but not a global destabilization of gene expression in dissected cerebellar external granule cell layer. Altogether these results strongly suggest that the three-copy genes are directly responsible for the phenotype present in cerebellum. We provide a short list of candidate genes.
keyword : Microarray
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Submitted on : Wednesday, October 22, 2008 - 8:00:00 AM
Last modification on : Thursday, November 18, 2021 - 4:06:24 AM
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  • HAL Id : pastel-00004252, version 1


Julien Laffaire. Modifications du transcriptome au cours du développement postnatal du cervelet dans un modèle murin de Trisomie 21. Sciences du Vivant [q-bio]. Université Pierre et Marie Curie - Paris VI, 2008. Français. ⟨pastel-00004252⟩



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