PUBLICATION

A Zebrafish Acromegaly Model Elevates DNA Damage and Impairs DNA Repair Pathways

Authors
Elbialy, A., Asakawa, S., Watabe, S., Kinoshita, S.
ID
ZDB-PUB-181020-21
Date
2018
Source
Biology   7(4): (Journal)
Registered Authors
Kinoshita, Shigeharu, Watabe, Shugo
Keywords
DNA damage, DNA repair, acromegaly, growth hormone
Datasets
GEO:GSE113169
MeSH Terms
none
PubMed
30336646 Full text @ Biology (Basel)
Abstract
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.
Genes / Markers
Marker Marker Type Name
eef1a1l1GENEeukaryotic translation elongation factor 1 alpha 1, like 1
gh1GENEgrowth hormone 1
igf1GENEinsulin-like growth factor 1
igf3GENEinsulin-like growth factor 3
tp53GENEtumor protein p53
1 - 5 of 5
Show
Figures
Figure Gallery (3 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kj39TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    Human Disease Fish Conditions Evidence
    acromegalykj39Tgstandard conditionsTAS
    1 - 1 of 1
    Show
    Sequence Targeting Reagents
    No data available
    Fish
    1 - 2 of 2
    Show
    Antibodies
    Name Type Antigen Genes Isotypes Host Organism
    Ab11-h2afxmonoclonal
      IgGRabbit
      1 - 1 of 1
      Show
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRed2EFGDsRed2
      1 - 1 of 1
      Show
      Mapping
      No data available