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GSE19677
Mus musculus
18 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
Evaluation of transcriptional changes in the striatum may be an effective approach to understanding the natural history of changes in expression contributing to the pathogenesis of Huntington disease (HD). We have performed genome-wide expression profiling of the YAC128 transgenic mouse model of HD at 12 and 24 months of age using two platforms in parallel; Affymetrix and Illumina. We performed gene expression profiling on the same striatal mRNA across both platforms.
Publication Title
Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. 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 and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2(Q150/Q150), 18-month Hdh(Q92/Q92) and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials.
Publication Title
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. 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 and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2(Q150/Q150), 18-month Hdh(Q92/Q92) and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials.
Publication Title
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
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, Huntingtons 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.
Publication Title
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Publication Title
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Publication Title
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Publication Title
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Sample Metadata Fields
Genetic information
View Samples- Saccharomyces cerevisiae
- 18 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Sky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Publication Title
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Sample Metadata Fields
Genetic information
View Samples