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Updated: Nov 8, 2025
Standardized Methods for Measuring Induction of the Heat Shock Response in Caenorhabditis elegans
Published on: July 3, 2020
The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1
Casandra Gomez-Paredes1, Michael A Mason1, Bridget A Taxy1
1Huntington's Disease Centre, Department of Neurodegenerative Disease and UK Dementia Research Institute at UCL, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.
Insights
Huntington's disease (HD) impairs the heat shock response, crucial for protein folding. A new assay reveals this impairment is similar in different mouse models, not due to reduced HSF1 levels.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansion, leading to huntingtin protein aggregation and inclusion bodies.
- Impaired heat shock response (HSR) is observed in HD progression, potentially worsening protein-folding pathology.
- Understanding HSR dysfunction is critical for developing therapeutic strategies for HD.
Purpose of the Study:
- To develop and validate a multiplex assay for simultaneous measurement of HSR gene expression in mouse tissues.
- To comprehensively analyze HSR impairment in different brain regions and peripheral tissues in HD mouse models.
- To investigate the role of HSF1 levels in the observed HSR impairment.
Main Methods:
- Development and validation of a 16-plex QuantiGene assay for simultaneous gene expression analysis.
- Pharmacological activation of the HSR in vivo in zQ175 and R6/2 mouse models of HD.
- Quantitative measurement of Hsf1 and nine heat shock genes in tibialis anterior, brain hemispheres, striatum, and cortex.
Main Results:
- The QuantiGene assay effectively measured HSR gene expression in mouse tissues.
- Pharmacological HSR activation revealed comparable impairment in tibialis anterior, brain hemispheres, and striatum of zQ175 and R6/2 mice.
- HSR impairment was detected in R6/2 cortex but not in zQ175 cortex, suggesting region-specific differences. HSF1 levels were not reduced, contradicting previous reports.
Conclusions:
- The developed QuantiGene assay provides a rapid and comprehensive tool for studying HSR in HD mouse models.
- HSR impairment in HD is comparable across specific tissues but shows regional variation in the brain.
- The study rules out reduced HSF1 levels as the cause of HSR impairment in these HD models.
Abstract:
Huntington's disease (HD) is a devastating neurodegenerative disorder, caused by a CAG/polyglutamine repeat expansion, that results in the aggregation of the huntingtin protein, culminating in the deposition of inclusion bodies in HD patient brains. We have previously shown that the heat shock response becomes impaired with disease progression in mouse models of HD. The disruption of this inducible arm of the proteostasis network is likely to exacerbate the pathogenesis of this protein-folding disease. To allow a rapid and more comprehensive analysis of the heat shock response, we have developed, and validated, a 16-plex QuantiGene assay that allows the expression of Hsf1 and nine heat shock genes, to be measured directly, and simultaneously, from mouse tissue. We used this QuantiGene assay to show that, following pharmacological activation in vivo, the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. In contrast, although a heat shock impairment could be detected in R6/2 cortex, this was not apparent in the cortex from zQ175 mice. Whilst the mechanism underlying this impairment remains unknown, our data indicated that it is not caused by a reduction in HSF1 levels, as had been reported.
