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Series GSE25232 Query DataSets for GSE25232
Status Public on Jan 01, 2011
Title In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons
Organism Mus musculus
Experiment type Expression profiling by array
Summary Huntington’s disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to neuronal dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared to those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support, among others. While genes related to excitotoxicity, dopamine signaling and trophic support, were altered in both DE5 and R6/2 transgenic mice, which may be either cell-autonomous or non-cell-autonomous,, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell autonomous mechanisms Overall, our results demonstrate that HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt,,such that mutant Htt-induced effects in cortical neurons is not necessary for striatal dysfunction/degeneration.
Overall design Striatum from DE5 transgenic mice vs. wt littermate controls
Contributor(s) Ehrlich ME, Kim S, Brown TB, Coppola G, Thomas EA, Geschwind D
Citation(s) 21177255
Submission date Nov 09, 2010
Last update date Jun 14, 2018
Contact name Elizabeth A. Thomas
Organization name The Scripps Research Institute
Department Molecular Biology
Street address 10550 N. Torrey Pines Rd
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (7)
GSM630828 wt_rep1
GSM630829 wt_rep2
GSM630830 wt_rep3
BioProject PRJNA134475

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE25232_RAW.tar 3.1 Mb (http)(custom) TAR
GSE25232_non-normalized_data.txt.gz 2.2 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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