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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 23, 2009 |
| Title |
Transcriptional analysis of murine neurobastoma N18 cell line transfected with a pAd-Dyrk1a vector |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The molecular mechanisms that lead to the cognitive defects characteristic of Down syndrome (DS), the most frequent cause of mental retardation, have remained elusive. Here we use a transgenic DS mouse model to show that DYRK1A gene dosage imbalance deregulates chromosomal clusters of genes located near neuron-restrictive silencer factor (REST/NRSF) binding sites. We found that DYRK1A binds the SWI/SNF-complex known to interact with REST/NRSF. Mutation of a REST/NRSF binding site in the promoter of the REST/NRSF target gene L1cam modifies the transcriptional effect of Dyrk1A-dosage imbalance on L1cam. DyrkA dosage imbalance perturbs Rest/Nrsf levels with decreased Rest/Nrsf expression in embryonic neurons and increased expression in adult neurons. We identified a coordinated deregulation of multiple genes that are responsible for the cellular phenotypic traits present in DS such as dendritic growth impairment and microcephaly during prenatal cortex development. Dyrk1a overexpression in primary mouse cortical neurons reduced the neuritic complexity. In the postnatal hippocampus, DYRK1A overexpression suppresses a form of synaptic plasticity that may be sufficient to cause DS cognitive defects. We propose that DYRK1A overexpression-related neuronal gene deregulation generates the brain phenotypic changes that characterize DS, with an accessory role for the gene dosage imbalance of other chromosome 21 genes.
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| Overall design |
Agilent Whole Mouse Genome oligomicroarrays (GEO accession no. GPL2872, Agilent Technologies, Palo Alto, CA) were used. They contain 60-mer DNA probes synthesized in situ in a 44k format. Of 44,290 spots, 2756 are controls. The remaining 41,534 spots represent 33,661 unique transcripts which correspond to 20,202 unique human genes. Five independent (Dyrk1A overexpression, five individual samples) measurements were carried out for each group of biological conditions using exchanged dye-labeled RNA targets (i.e., Cy3 and Cy5 dye-swapping experiments).
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| Contributor(s) |
Lepagnol-Bestel A, Zvara A, Maussion G, Quignon F, Ngimbous B, Ramoz N, Imbeaud S, Loe-Mie Y, Benihoud K, Agier N, Salin PA, Cardona A, Khung-Savatovsky S, Kallunki P, Delabar J, Puskas LG, Delacroix H, Aggerbeck L, Delezoide A, Delattre O, Gorwood P, Moalic J, Simonneau M |
| Citation(s) |
19218269, 20457675 |
| Submission date |
Dec 18, 2008 |
| Last update date |
Dec 06, 2012 |
| Contact name |
Gilles Maussion |
| Organization name |
INSERM U675
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| Street address |
16 rue Henri Huchard
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| City |
PARIS |
| ZIP/Postal code |
75018 |
| Country |
France |
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| Platforms (1) |
| GPL2872 |
Agilent-012694 Whole Mouse Genome G4122A (Feature Number version) |
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| Samples (5)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA114541 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE14030_RAW.tar |
37.7 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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