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GSE55177
Mus musculus
67 Downloadable Samples
Description
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder, which is caused by an unstable CAG-repeat expansion in the SCA2 gene, that encodes a polyglutamine tract (polyQ-tract) expansion in ataxin-2 protein (ATXN2). The RNA-binding protein ATXN2 interacts with the poly(A)-binding protein PABPC1, localizing to ribosomes at the rough endoplasmic reticulum or to polysomes. Under cell stress ATXN2 and PABPC1 show redistribution to stress granules where mRNAs are kept away from translation and from degradation. It is unknown whether ATXN2 associates preferentially with specific mRNAs or how it modulates their processing. Here, we investigated Atxn2 knock-out (Atxn2-/-) mouse liver, cerebellum and midbrain regarding their RNA profile, employing oligonucleotide microarrays for screening and RNA deep sequencing for validation. Modest ~1.4-fold upregulations were observed for the level of many mRNAs encoding ribosomal proteins and other translation pathway factors. Quantitative reverse transcriptase PCR and immunoblots in liver tissue confirmed these effects and demonstrated an inverse correlation also with PABPC1 mRNA and protein. ATXN2 deficiency also enhanced phosphorylation of the ribosomal protein S6, while impairing the global protein synthesis rate, suggesting a block between the enhanced translation drive and the impaired execution. Furthermore, ATXN2 overexpression and deficiency retarded cell cycle progression. ATXN2 mRNA levels showed a delayed phasic twofold increase under amino acid and serum starvation, similar to ATXN3, but different from motor neuron disease genes MAPT and SQSTM1. ATXN2 mRNA levels depended particularly on mTOR signalling. Altogether the data implicate ATXN2 in the adaptation of mRNA translation and cell growth to nutrient availability and stress.
Publication Title
Genetic ablation of ataxin-2 increases several global translation factors in their transcript abundance but decreases translation rate.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Mutations of the transcriptional regulator Mecp2 cause the X-linked autism spectrum disorder Rett syndrome (RTT), and Mecp2 has been implicated in several other neurodevelopmental disorders. To identify potential target genes regulated directly or indirectly by MeCP2, we performed comparative gene expression analysis via oligonucleotide microarrays on Mecp2-/y (Mecp2-null) and wild-type CPN purified via fluorescence-activated cell sorting (FACS).
Publication Title
Reduction of aberrant NF-κB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
Description
Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts.
Publication Title
Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone.
Sample Metadata Fields
Specimen part
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