Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression signature of cerebellum hypoplasia in a mouse model of Down syndrome (Part I).

ABSTRACT: We designed a large scale gene expression study in Ts1Cje mice between P0 and P10 in order to measure the effects of trisomy 21 on a large number of samples (56 in total) in a tissue that is affected in Down syndrome (the cerebellum) and to quantify the defect during development in order to correlate gene expression changes to the phenotype observed. Keywords: Down syndrome, Ts1Cje, cerebellum, development, hypoplasia We analyzed gene expression in the cerebellum of Ts1Cje and euploid mice at P0, P3, P7 and P10 using pangenomic two colors microarrays containing 25 344 probes representing approximately 15 574 mouse genes. 56 samples from individual cerebellum were hybridized on 28 microarrays. On each microarray we hybridized a Ts1Cje sample versus an euploid sample and always a male versus a female. In addition on the same microarray we always compared samples from mice of the same age or with a maximum difference of 4 days (P0 versus P3, P3 versus P7 or P7 versus P10).

ORGANISM(S): Mus musculus

SUBMITTER: Julien Laffaire

PROVIDER: E-GEOD-11448 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development.

Laffaire Julien J Rivals Isabelle I Dauphinot Luce L Pasteau Fabien F Wehrle Rosine R Larrat Benoit B Vitalis Tania T Moldrich Randal X RX Rossier Jean J Sinkus Ralph R Herault Yann Y Dusart Isabelle I Potier Marie-Claude MC

BMC genomics 20090330

<h4>Background</h4>Down syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. The mechanisms by which this aneuploidy produces the complex and variable phenotype observed in people with Down syndrome are still under discussion. Recent studies have demonstrated an increased transcript level of the three-copy genes with some dosage compensation or amplification for a subset of them. The impact of this gene dosage effect on the whole transcriptome is still deba ...[more]

PMID: 19331679

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Project description:Recombinant tissue-type plasminogen activator (tPA) is the fibrinolytic drug of choice to treat stroke patients. However, a growing body of evidence indicates that besides its beneficial thrombolytic role, tPA can also have a deleterious effect on the ischaemic brain. Although ageing influences stroke incidence, complications and outcome, age-dependent relationships between endogenous tPA and stroke injuries have not been investigated yet. Here, we report that ageing is associated with a selective lowering of brain tPA expression in the murine brain. Moreover, our results show that albumin D site-binding protein (DBP) as a key age-associated regulator of the neuronal transcription of tPA. Additionally, inhibition of DBP-mediated tPA expression confers in vitro neuroprotection. Accordingly, reduced levels of tPA in old mice are associated with smaller excitotoxic/ischaemic injuries and protection of the permeability of the neurovascular unit during cerebral ischaemia. Likewise, we provide neuroradiological evidence indicating the existence of an inverse relationship between age and the volume of the ischaemic lesion in patients with acute ischaemic stroke. Together, these results indicate that the relationship among DBP, tPA and ageing play an important role in the outcome of cerebral ischaemia. For each stage (4 months and 21 months), samples were prepared by pooling an equal amount of the 3 individual RNA. Five M-BM-5g of total RNA from each pool were reverse-transcribed in the presence of 7.5M-BM-5M random hexamers (GE Healthcare), 75M-BM-5M aminoallyl-dUTP (Sigma-Aldrich) and 100U Rtases Reverse-iT Blend (Thermo scientific) overnight at 37M-BM-0C. Aminoallyl cDNAs were then labelled with Cy5 or Cy3 mono-Reactive Dye (GE Healthcare) according to the manusfacturerM-bM-^@M-^Ys instructions. Labelled cDNAs were then purified on Qiaquick PCR prurification kit (Qiagen) and hybridized to the RNG-MRC_MM25k_EVRY microarrays (Le brigand et al., NAR, 2006) according to the RNG procedures (http://www.microarray.fr:8080/merge/index). Each pool was hybridized in duplicate dye-swap independent experiments. After hybridization, median signal and median background intensities were extracted using Genepix 4.1 software (Axon Instruments). We have first evaluated the level of expression of each gene by calculating the mean ratio M-bM-^@M-^\signal/backgroundM-bM-^@M-^] for each corresponding spot from the 2 dye-swap experiments. Genes were considered to be expressed if their mean ratio was higher or equal to 1.2. Genes with mean ratio < 1.2 in the 2 conditions were not used for further analysis. These filtered data were then submitted to VARAN (http//:www. bionet. espci.fr) for normalization by lowess fit and differential expression analysis (Golfier et al., 2004). Normalized log2ratio 21 months/4 months were then used for further statistical analysis by SAM software (Tusher et al., 2001) and t-test with a p-value equal to 5% using TIGR Multiexperiment Viewer (TM4:MeV, http://www.tm4.org/mev.html). The final list of differentially expressed genes was established by comparing the results obtained with the 3 methods.

Dataset Information

Gene expression signature of cerebellum hypoplasia in a mouse model of Down syndrome (Part I).

Publications

Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development.

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