Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of mouse Ts1Cje (mouse model of Down syndrome) and euploids murine cerebellum during postnatal development

ABSTRACT: Transcriptome analysis of Ts1Cje (mouse model of Down syndrome) and euploids murine cerebellum during postnatal development Keywords = Down syndrome Keywords = Chromosome 21 Keywords = Transcriptome Keywords = Microarray Keywords = Cerebellum Keywords = Development Keywords: other

ORGANISM(S): Mus musculus

SUBMITTER: Luce Dauphinot

PROVIDER: E-GEOD-1611 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome.

Dauphinot L L Lyle R R Rivals I I Dang M Tran MT Moldrich R X RX Golfier G G Ettwiller L L Toyama K K Rossier J J Personnaz L L Antonarakis S E SE Epstein C J CJ Sinet P-M PM Potier M-C MC

Human molecular genetics 20041208 3

The central nervous system of persons with Down syndrome presents cytoarchitectural abnormalities that likely result from gene-dosage effects affecting the expression of key developmental genes. To test this hypothesis, we have investigated the transcriptome of the cerebellum of the Ts1Cje mouse model of Down syndrome during postnatal development using microarrays and quantitative PCR (qPCR). Genes present in three copies were consistently overexpressed, with a mean ratio relative to euploid of ...[more]

PMID: 15590701

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Project description:Down syndrome is characterized by a complex phenotype that includes developmental disabilities and congenital anomalies emerging during fetal life. The molecular origin of these abnormalities is poorly understood. Despite the evidence of prenatal onset of the phenotype, most therapeutic trials have been conducted in affected adults. This study presents evidence for fetal brain molecular and neonatal behavioral abnormalities in the Ts1Cje mouse model of Down syndrome. Gene expression changes were more pronounced in the Ts1Cje fetal brains than adult cerebral cortex and hippocampus. Functional pathway analyses showed that Ts1Cje embryonic brains display significant up-regulation of cell cycle and down-regulation of Solute-carrier amino acid transport pathways. Several cellular processes, including apoptosis, inflammation, Jak/Stat signaling, G-protein signaling and oxidoreductase activity were consistently dysregulated at both stages. Fetal brain gene expression changes were associated with early behavioral deficits in surface righting, cliff aversion, negative geotaxis, forelimb grasp, ultrasonic vocalization and homing tests. In combination with the human studies, this suggests that the Down syndrome phenotype manifests prenatally and provides a rationale for prenatal therapy to improve perinatal brain development and postnatal neurocognition. In the present study, we demonstrated that significant gene expression abnormalities were already present in the embryonic day 15 forebrain of the Ts1Cje mouse model of DS. The abnormal Ts1Cje embryonic molecular signature was associated with early postnatal developmental milestones and behavioral changes. These data provide a comprehensive picture of the genotype-phenotype relationship the Ts1Cje model of Down syndrome. We analyzed the forebrain whole transcriptome from embryonic day 15.5 (E15.5) Ts1Cje (n=5) and wild-type (n=5) using Affymetrix mouse gene 1.0 ST array. Data were normalized and analyzed to identify and accurately map genes that are significantly differentially expressed. Functional analyses were performed using GSEA and DAVID and DFLAT to better characterize cellular processes and pathways that are consistently affected in both brain regions. In separate experiments, the Fox scale, ultrasonic vocalization and homing tests were used to investigate postnatal behavioral deficits in Ts1Cje pups (n=29) versus WT littermates (n=64) at days 3 to 21.

Dataset Information

Transcription profiling by array of mouse Ts1Cje (mouse model of Down syndrome) and euploids murine cerebellum during postnatal development

Publications

The cerebellar transcriptome during postnatal development of the Ts1Cje mouse, a segmental trisomy model for Down syndrome.

Similar Datasets

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