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 differ 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.
The introgressed of pkIs2386 transgene [unc-54p::α-synuclein::YFP + unc-119(+)] from NL5901, which has an N2 genetic background, into the genetically divergent wild isolates JU1511, JU1926, JU1931, and JU1941. Synchronized starved L1 juveniles were inoculated on NGM plates with E.coli at 20°C. When N2 worms were observed to have reached the L4 stage, worms were transferred into the wells of a 96-well-plate, where each well contained 50μl of M9 buffer. Three biological replicates were undertaken, with 10 worms per well for 3–5 wells per genotype in each of the replicates. Activity was then measured in an 30 min period using a WMicrotracker.
In this work, differences between lines in movement were tested. The movement of worms in liquid (Fig. 3c) was assayed. These data indicate that N2 and NL5901 show similar movement rates and that the α-synuclein expressing lines expression shows reduced activity in comparison to their corresponding wild isolate. These data therefore indicate that the presence of an α-synuclein introgression produces a genotype-specific impact, likely a direct consequence ofα-synuclein expression in the body wall muscles.
BMC Genomics. 2019 Mar 20;20(1):232. doi: 10.1186/s12864-019-5597-1
Wang YA, Snoek BL, Sterken MG, Riksen JAG, Stastna JJ, Kammenga JE, Harvey SC.