Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 562812
Title Genetic background modifies phenotypic and transcriptional responses in a C. elegans model of α-synuclein toxicity
Author(s) Wang, Yiru; Snoek, Basten; Sterken, Mark; Riksen, Joost; Stastna, Jana J.; Kammenga, Jan; Harvey, Simon C.
Source Wageningen University and Research
DOI https://doi.org/10.6084/m9.figshare.c.4442933
Department(s) Laboratory of Nematology
Groep Koornneef
EPS
PE&RC
Publication type Dataset
Publication year 2019
Keyword(s) Natural variation - Gene expression profile - Protein aggregation - alfa-Synuclein - Genetic background - Caenorhabditis elegans
Abstract Accumulation of protein aggregates are a major hallmark of progressive neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. Transgenic Caenorhabditis elegans nematodes expressing the human synaptic protein α-synuclein in body wall muscle show inclusions of aggregated protein, which affects similar genetic pathways as in humans. It is not however known how the effects of α-synuclein expression in C. elegans differs among genetic backgrounds. Here, we compared gene expression patterns and investigated the phenotypic consequences of transgenic α-synuclein expression in five different C. elegans genetic backgrounds. 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.
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