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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 28, 2010 |
| Title |
Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The type III RNase Dicer is responsible for the maturation and function of microRNA (miRNA) molecules in the cell. It is now well documented that Dicer and the fine-tuning of the miRNA gene network are important for neuronal integrity. However, the underlying mechanisms involved in neuronal death, particularly in the adult brain, remain poorly defined. Here, we show that absence of Dicer in the adult forebrain is accompanied by a mixed neurodegenerative phenotype. While neuronal loss is observed in the hippocampus, cellular shrinkage is predominant in the cortex. Interestingly, neuronal degeneration coincides with the hyperphosphorylation of endogenous tau at several epitopes previously associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 as one of the candidate kinases responsible for this event in vivo. We further demonstrate that miRNAs belonging to the miR-15 family are potent regulators of ERK1 expression in mouse neuronal cells and co-expressed with ERK1/2 in vivo. Last, we show that miR-15a is specifically downregulated in Alzheimer’s disease brain. In sum, these results support the hypothesis that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation.
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| Overall design |
Dicer KO vs. control
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| Contributor(s) |
Hebert SS, Papadopoulou AS, Smith P, Galas MC, Planel E, Silahtaroglu AN, Sergeant N, Buee L, De Strooper b |
| Citation(s) |
20660113 |
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| Submission date |
Aug 27, 2010 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Ezequiel L Calvo |
| E-mail(s) |
[email protected]
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| Organization name |
CRCHUL
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| Department |
Molecular Endocrinilogy
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| Lab |
Microarrays
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| Street address |
2705 Boul. Laurier
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| City |
Quebec |
| State/province |
Quebec |
| ZIP/Postal code |
G1V 4G2 |
| Country |
Canada |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM587916 |
Mouse cortex of Dicer KO mice, biological rep1 |
| GSM587917 |
Mouse cortex of Dicer KO mice, biological rep2 |
| GSM587918 |
Mouse cortex of Dicer KO mice, biological rep3 |
| GSM587919 |
Mouse cortex of control mice, biological rep1 |
| GSM587920 |
Mouse cortex of control mice, biological rep2 |
| GSM587921 |
Mouse cortex of control mice, biological rep3 |
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| Relations |
| BioProject |
PRJNA130667 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE23847_RAW.tar |
25.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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