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Series GSE10202 Query DataSets for GSE10202
Status Public on Jan 25, 2008
Title Striatal gene expression data from 22-month-old CHL2 mice and control mice.
Organism Mus musculus
Experiment type Expression profiling by array
Summary Achieving a mechanistic understanding of disease and initiating preclinical therapeutic trials necessitate the study of huntingtin toxicity and its remedy in model systems. To allow the engagement of appropriate experimental paradigms, Huntington’s disease (HD) models need to be validated in terms of how they recapitulate a particular aspect of human disease. In order to examine transcriptome-related effects of mutant huntingtin, we compared striatal mRNA profiles from seven genetic mouse models of disease to that of postmortem human HD caudate using microarray analysis. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in models of HD took longer to appear, 15-month and 22-month CHL2Q150/Q150, 18-month HdhQ92/Q92 and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. When the affected genes were compared across models, a robust concordance was observed. Importantly, changes concordant across multiple lines mice were also in excellent agreement with the mRNA changes seen in human HD caudate. Although it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared to those caused by expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. There was, however, an overall concordance between transcriptomic signature and disease stage. We thus conclude that the transcriptional changes of HD can be modelled in several available lines of transgenic mice, comprising lines expressing both N-terminal and full-length mutant huntingtin proteins. The combined analysis of mouse and human HD transcriptomes provides an important chronology of mutant huntingtin's gene expression effects.
Keywords: genetic modification
Overall design Striatal samples from 4 CHL2 Q150/Q150 mutant mice and 4 age-matched wild-type mice.
Contributor(s) Kuhn A, Sathasivam K, Bates GP, Luthi-Carter R
Citation(s) 17519223
Submission date Jan 18, 2008
Last update date Feb 11, 2019
Contact name Alexandre Kuhn
Organization name NIH
Department NIA
Lab Laboratory of Neurogenetics
Street address 35 Convent Dr
City Bethesda
State/province MD
ZIP/Postal code 20892-3707
Country USA
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (8)
GSM257680 striatum_CHL2_22m_141
GSM257681 striatum_CHL2_22m_153
GSM257682 striatum_CHL2_22m_154
This SubSeries is part of SuperSeries:
GSE10263 Mutant huntingtin's effects on striatal gene expression in mice
BioProject PRJNA108999

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
GSE10202_RAW.tar 47.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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