ArticleNucleic acids research2015
Zebrafish lacking functional DNA polymerase gamma survive to juvenile stage, despite rapid and sustained mitochondrial DNA depletion, altered energetics and growth.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Model systems informing mechanisms and drug discovery: a review ofWellcome open research · 2023Pooled it
- Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis.Journal of cellular physiology · 2026Article
- Non-Mammalian Models for Mitochondria Research in CNS Disorders.Biomolecules · 2026Review
- Nucleotide metabolic rewiring enables NLRP3 inflammasome hyperactivation in obesity.Science (New York, N.Y.) · 2026Article
- Model organisms in POLG-related disorders: insights from yeast to multicellular systems.Cell death & disease · 2025Review
- Deoxynucleoside supplementation ameliorates the disease associated phenotypes in a zebrafish model of RRM2B mtDNA depletion syndrome.Human molecular genetics · 2025Article
- Zebrafish polg2 knock-out recapitulates human POLG-disorders; implications for drug treatment.Cell death & disease · 2024Article
- PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis.Cancer cell international · 2023Article
- Mitochondrial damage and activation of the cytosolic DNA sensor cGAS-STING pathway lead to cardiac pyroptosis and hypertrophy in diabetic cardiomyopathy mice.Cell death discovery · 2022Article
- DTYMK is essential for genome integrity and neuronal survival.Acta neuropathologica · 2022Article
- Mapping Adverse Outcome Pathways for Kidney Injury as a Basis for the Development of Mechanism-Based Animal-Sparing Approaches to Assessment of Nephrotoxicity.Frontiers in toxicology · 2022Article
- Sirt1 promotes tissue regeneration in zebrafish through regulating the mitochondrial unfolded protein response.iScience · 2021Article
- Therapy Prospects for Mitochondrial DNA Maintenance Disorders.International journal of molecular sciences · 2021Review
- Zebrafish Models of Autosomal Recessive Ataxias.Cells · 2021Review
- Efficient clofilium tosylate-mediated rescue of POLG-related disease phenotypes in zebrafish.Cell death & disease · 2021Article
- The zebrafish orthologue of the human hepatocerebral disease geneDisease models & mechanisms · 2019Article
- Nucleoside supplementation modulates mitochondrial DNA copy number in the dguok -/- zebrafish.Human molecular genetics · 2019Article
- Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish.PLoS genetics · 2018Article
- Metabolic etiologies in West syndrome.Epilepsia open · 2018Review
- Inherited mitochondrial genomic instability and chemical exposures.Toxicology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
DNA polymerase gamma (POLG) is essential for replication and repair of mitochondrial DNA (mtDNA). Mutations in POLG cause mtDNA instability and a diverse range of poorly understood human diseases. Here, we created a unique Polg animal model, by modifying polg within the critical and highly conserved polymerase domain in zebrafish. polg(+/-) offspring were indistinguishable from WT siblings in multiple phenotypic and biochemical measures. However, polg(-/-) mutants developed severe mtDNA depletion by one week post-fertilization (wpf), developed slowly and had regenerative defects, yet surprisingly survived up to 4 wpf. An in vivo mtDNA polymerase activity assay utilizing ethidium bromide (EtBr) to deplete mtDNA, showed that polg(+/-) and WT zebrafish fully recover mtDNA content two weeks post-EtBr removal. EtBr further reduced already low levels of mtDNA in polg(-/-) animals, but mtDNA content did not recover following release from EtBr. Despite significantly decreased respiration that corresponded with tissue-specific levels of mtDNA, polg(-/-) animals had WT levels of ATP and no increase in lactate. This zebrafish model of mitochondrial disease now provides unique opportunities for studying mtDNA instability from multiple angles, as polg(-/-) mutants can survive to juvenile stage, rather than lose viability in embryogenesis as seen in Polg mutant mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.