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Biology 2018, 7(4), 47; https://doi.org/10.3390/biology7040047

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

1
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo, Tokyo 113-8657, Japan
2
Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
3
School of Marine Biosciences, Kitasato University, Minami, Sagamihara, Kanagawa 252-0313, Japan
*
Author to whom correspondence should be addressed.
Received: 10 September 2018 / Revised: 15 October 2018 / Accepted: 15 October 2018 / Published: 17 October 2018
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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. View Full-Text
Keywords: growth hormone; acromegaly; DNA damage; DNA repair growth hormone; acromegaly; DNA damage; DNA repair
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Elbialy, A.; Asakawa, S.; Watabe, S.; Kinoshita, S. A Zebrafish Acromegaly Model Elevates DNA Damage and Impairs DNA Repair Pathways. Biology 2018, 7, 47.

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