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| Status |
Public on Apr 19, 2022 |
| Title |
Investigation of genetic compensation in tdp1-/- zebrafish embryos |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by array
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| Summary |
Tdp1, tyrosyl-DNA phosphodiesterase 1, is an enzyme responsible for the repair of DNA breaks resulting from aberrant topoisomerase 1 activity, called Top1 cleavage complexes (Top1-CCs). Mutation of Tdp1 leads to a progressive neurodegenerative disorder spinocerebellar ataxia with axonal neuropathy 1 (SCAN1). We have generated tdp1-/- zebrafish as a model for SCAN1. The adult fish have a behavioral defect and hypersensitivity to camptothecin (CPT), a Top1 poison. Strikingly, the embryos do not show increased sensitivity to CPT, unlike any other reported vertebrate models, suggesting genetic compensation is at play at this stage.
We thus carried out microarray analysis in CPT-treated zebrafish embryos to compare the gene expression profiles of tdp1WT and tdp1-/- genotypes. Gene expression analysis revealed 1,8111 genes that were differentially expressed: 1,071 were upregulated and 740 were downregulated. Sprtn and neil1, two potential compensation candidates were upregulated in the tdp1-/- embryos.
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| Overall design |
Gene expression profiling utilized total RNA extracted from whole zebrafish embryo lysate from 5 dpf tdp1WT and tdp1-/- embryos, treated with 500 nM CPT for 16h 4-5dpf.
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| Contributor(s) |
Zaksauskaite R, Heath PR, van Eeden F, El-Khamisy S |
| Citation(s) |
33514542 |
| Submission date |
Apr 20, 2020 |
| Last update date |
Aug 01, 2022 |
| Contact name |
Sherif El-Khamisy |
| E-mail(s) |
S.El-Khamisy@sheffield.ac.uk
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| Organization name |
The University of Sheffield
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| Department |
Department of Molecular Biology and Biotechnology
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| Street address |
Firth Court, Western Bank
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| City |
Sheffield |
| State/province |
South Yorkshire |
| ZIP/Postal code |
S10 2TN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL16933 |
[ZebGene-1_0-st] Zebrafish Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA626551 |
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