Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression Profile Of A Caenorhabditis Elegans Model Of Adult Onset Neuronal Ceroid Lipofuscinosis Reveals Down Regulation Of Ubiquitin E3 Ligase Components.

ABSTRACT: Transcriptional profiling of two C. elegans mutants of dnj-14, the worm homolog of cysteine string protein (CSP), compared to two control strains N2 (Bristol) and CZ1200. CSP is a neuroprotective protein and the C. elegans mutants, tm3223 and ok237, are used to model the neurodegenerative disease, adult onset neuronal ceroid lipofucinosis (ANCL), which can occur as a result of mutations in the human CSP gene, DNAJC5. It is hoped that transcriptional profiling of these mutants might help to identify novel therapeutic targets for neurodegerative diseases such as ANCL.

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Hannah McCue

PROVIDER: E-MTAB-3147 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Expression profile of a Caenorhabditis elegans model of adult neuronal ceroid lipofuscinosis reveals down regulation of ubiquitin E3 ligase components.

McCue Hannah V HV Chen Xi X Barclay Jeff W JW Morgan Alan A Burgoyne Robert D RD

Scientific reports 20150923

Cysteine string protein (CSP) is a chaperone of the Dnaj/Hsp40 family of proteins and is essential for synaptic maintenance. Mutations in the human gene encoding CSP, DNAJC5, cause adult neuronal ceroid lipofucinosis (ANCL) which is characterised by progressive dementia, movement disorders, seizures and premature death. CSP null models in mice, flies and worms have been shown to also exhibit similar neurodegenerative phenotypes. Here we have explored the mechanisms underlying ANCL disease progre ...[more]

PMID: 26395859

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Project description:The two major methods for growing C. elegans are liquid and plate culture. Differences in oxygenation and other environmental variables could affect many experimentally relevant biological processes, such as metabolism, cellular structure, and gene regulation. Worms on solid support move with deliberate sinusoidal movements, while worms in liquid thrash rapidly and almost constantly, often appearing elongated. We investigated differential gene expression under these two commonly used growth conditions. Embryos were isolated from adults grown on plates. After hatching, animals were placed either on plates or in liquid under standard conditions, and grown until young adulthood, approximately 48 hours later. RNA was isolated independently from each growth, differentially labeled with a fluorescent dye, and mixed directly for comparative hybridization to NimbleGen DNA microarrays, which contained probes designed to measure expression from all predicted C. elegans coding genes. The experiment was performed in triplicate. Analysis of the expression data yielded surprisingly few genes with differential expression, about 1%. Overall, 176 genes were downregulated significantly (p<0.01; Student's t) in liquid culture relative to plates, but of these only 102 genes were down two-fold or more. A total of 121 genes were upregulated (p<0.01. Student's t) in liquid; of these, RNA corresponding to 50 increased by at least two-fold. Surprisingly few genes directly associated with a stress response were differentially regulated in this experiment. However, the single gene most strongly upregulated in liquid is nnt-1, which encodes a mitochondrial NADP transhydrogenase, which protects against oxidative stress (Arkbladt et al., 2005 PMID: 15890626). Other molecules associated with reducing oxidation are also upregulated in liquid culture, including thioredoxin, and two glutathione-S-transferases. As a class, however, the group of genes most differentially regulated encode collagens. A total of 12 collagen genes were downregulated in liquid culture relative to plates, while none are upregulated. Other genes affected include those encoding proteins involved in ubiquitin-mediated proteolysis, Ras signaling, transcriptional regulation, ribosome function, and multiple membrane-associated proteins. The limited changes in relative RNA levels under different culture conditions provide increased confidence in comparisons made between worms grown in liquid and solid culture, and more generally between datasets obtained in different labs under slightly different culture conditions. Knowing which genes are most responsive to different culture conditions inform us about how environment affects the animal, and should be of interest for comparison to other stress and longevity global datasets. Total RNA was extracted from young adult hermaphrodite C. elegans grown either in s-basal liquid cultures or nematode growth medium plates under standard conditions.

Dataset Information

Expression Profile Of A Caenorhabditis Elegans Model Of Adult Onset Neuronal Ceroid Lipofuscinosis Reveals Down Regulation Of Ubiquitin E3 Ligase Components.

Publications

Expression profile of a Caenorhabditis elegans model of adult neuronal ceroid lipofuscinosis reveals down regulation of ubiquitin E3 ligase components.

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