Gene expression profile in a C. elegans model of Alpha-Synuclein with variable natural genetic background and their phenotypic variations

Yiru A. Wang, L.B. Snoek, M.G. Sterken, J.A.G. Riksen, Jana J. Stastna, J.E. Kammenga, S. Harvey

Research output: Contribution to conferencePosterAcademic

Abstract

α-synuclein plays a key role in progressive degeneration in the human nervous system which underlies Parkinson’s disease (PD). The nematode C. elegans is an excellent model for studying α-synuclein associated molecular mechanisms due to the high level of conservation of gene functions compared to humans. Until recently, C. elegans research has mostly relied on a single genotype – the canonical N2 strain – limiting the ability to explore how naturally varying alleles alter pathological mechanisms in neurodegeneration. Hence, we employ transgenic C. elegans worms containing the introgressed human copy of α-synuclein in five different genetic backgrounds. Analysis of these transgenic introgressed lines indicates that transgene (unc-54:: α-Syn:: YFP) effects vary greatly depending on the background. To understand the genetic bases of these phenotypic differences, we measured various phenotypic traits and investigated gene expression differences by microarray. These analyses identified genes that are up- and down-regulated in all genotypes and genes expressed at a specific stage to particular genetic backgrounds. Functional enrichment links these genes to the aggregation of α-synuclein, also to the associated developmental arrest, metabolic, and cellular repair mechanisms. There are also other phenotypic variations related to α-synuclein accumulation, including the genotype-specific on lifespan, developmental delay, mobility deficits, and feeding arrest.
Original languageEnglish
Publication statusPublished - May 2019
EventNWO Life sciences congress: Life2019 - Bunnik, Netherlands
Duration: 28 May 201929 May 2019

Conference

ConferenceNWO Life sciences congress
CountryNetherlands
CityBunnik
Period28/05/1929/05/19

Fingerprint Dive into the research topics of 'Gene expression profile in a C. elegans model of Alpha-Synuclein with variable natural genetic background and their phenotypic variations'. Together they form a unique fingerprint.

  • Cite this

    Wang, Y. A., Snoek, L. B., Sterken, M. G., Riksen, J. A. G., Stastna, J. J., Kammenga, J. E., & Harvey, S. (2019). Gene expression profile in a C. elegans model of Alpha-Synuclein with variable natural genetic background and their phenotypic variations. Poster session presented at NWO Life sciences congress, Bunnik, Netherlands.