Results - Transcriptome analysis indicates that α-synuclein expression effects pathways associated with nutrient storage, lipid transportation and ion exchange and that effects vary depending on the genetic background. These gene expression changes predict that a range of phenotypes will be affected by α-synuclein expression. We confirm this, showing that α-synuclein expression delayed development, reduced lifespan, increased rate of matricidal hatching, and slows pharyngeal pumping. Critically, these phenotypic effects depend on the genetic background and coincide with the core changes in gene expression.
Conclusions - Together, our results show genotype-specific effects and core alterations in both gene expression and in phenotype in response to α-synuclein expression. We conclude that the effects of α-synuclein expression are substantially modified by the genetic background, illustrating that genetic background needs to be considered in C. elegans models of neurodegenerative disease
- Caenorhabditis elegans
- Gene expression profile
- Genetic background
- Natural variation
- Protein aggregation
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Genetic background modifies phenotypic and transcriptional responses in a C. elegans model of α-synuclein toxicity
Wang, Y. (Creator), Snoek, B. (Creator), Sterken, M. (Creator), Riksen, J. (Creator), Stastna, J. J. (Creator), Kammenga, J. (Creator) & Harvey, S. C. (Creator), Wageningen University and Research, 20 Mar 2019
Microarray of five Caenorhabiditis elegans genotypes with or without a human alpha-synuclein transgene in the genetic background
Sterken, M. (Creator), Wageningen University & Research, 11 Feb 2019