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| Status |
Public on Nov 28, 2018 |
| Title |
A Zebrafish Acromegaly Model Elevates DNA Damage and Impairs DNA Repair Pathways |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Acromegaly is a pathological condition due to excess growth hormone (GH) secretion. Acromegaly patients exhibit a deterioration of health and many associated complications, such as cardiovascular issues, arthritis, kidney diseases, muscular weakness, and colon cancer. Since these complications are generalized throughout the body, we investigated the effect of GH excess on cellular integrity. Here, we established stable acromegaly model zebrafish lines that overexpress tilapia GH and the red fluorescence protein (RFP) reporter gene for tracking GH gene expression throughout generations, and performed RNA-Seq data analysis from different organs. Intriguingly, heatmap and Expression2Kinases (X2K) analysis revealed the enrichment of DNA damage markers in various organs. Moreover, H2A.X immunostaining analysis in acromegaly zebrafish larvae and the adult acromegaly model brain and muscle showed a robust increase in the number of DNA-damaged cells. Using Gene Set Enrichment Analysis (GSEA), we found that the acromegaly zebrafish model had impaired DNA repair pathways in the liver, such as double-strand break (DSB), homologous recombination repair (HRR), non-homologous end joining (NHEJ), nucleotide excision repair (NER), and translesion synthesis (TLS). Interestingly, the impairment of DNA repair was even more prominent in acromegaly model than in aged zebrafish (three years old). Thus, our study demonstrates that affection of cellular integrity is characteristic of acromegaly
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| Overall design |
Total mRNA obtained from 1-years old acromegaly zebrafish model muscle, brain, kidney, liver and 3-day old larvae compared to wild-type (WT) zebrafish were generated by deep sequencing using Illumina.
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| Contributor(s) |
Elbialy AK, Kinoshita S, Asakawa S |
| Citation(s) |
30336646, 32517323, 33849304 |
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| Submission date |
Apr 16, 2018 |
| Last update date |
May 12, 2021 |
| Contact name |
Shigeharu Kinoshita |
| Organization name |
The University of Tokyo
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| Department |
Aquatic Bioscience
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| Lab |
Aquatic Molecular Biology and Biotechnology
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| Street address |
1-1-1,Yayoi, Bunkyo, Tokyo, 113-8657 Japan room 251
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| City |
Tokyo |
| State/province |
Bunkyo |
| ZIP/Postal code |
113-8657 |
| Country |
Japan |
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| Platforms (1) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA450343 |
| SRA |
SRP140471 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113169_All_samples_FPKM_values.txt.gz |
44.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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