Subject collection: Zebrafish as a Disease Model
- Genetic variation in GNB5 causes bradycardia by augmenting the cholinergic response via increased acetylcholine-activated potassium current (IK,ACh)
Summary: The authors show hiPSC-cardiomyocyte-based modeling of a mutation in a G-protein β-subunit that affects the electrophysiological response of cardiomyocytes to the cholinergic regulation of the heart rate, uncovering a potential therapy for severe bradycardia in humans carrying these mutations.
- Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration
Summary: In a zebrafish model for inflammation, glucocorticoids do not affect the migration of macrophages, but inhibit their differentiation towards an M1 phenotype, by strongly attenuating transcriptional responses in these cells.
- Vascular defects of DYRK1A knockouts are ameliorated by modulating calcium signaling in zebrafish
Summary: The roles of DYRK1A in angiogenesis and maintenance of the developing cerebral vasculature mediated by calcium signaling were revealed using zebrafish dyrk1aa knockout mutants.
- Disruption of asxl1 results in myeloproliferative neoplasms in zebrafish
Summary: Homozygous loss of asxl1 in zebrafish leads to apoptosis of newly formed HSCs by upregulation of bim and bid. Half of the asxl1+/− zebrafish had MPNs by 5 months of age.
- Enhancing regeneration after acute kidney injury by promoting cellular dedifferentiation in zebrafish
Summary: Mortality associated with AKI is in part due to limited treatments available to ameliorate injury. The authors identify a compound that accelerates AKI recovery and promotes cellular dedifferentiation.
- Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone
Summary: Acute exposure to 1,4-benzoquinone leads to lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood, resembling benzene-induced cytopenia and myeloid dysplasia in humans.
- The zebrafish orthologue of the human hepatocerebral disease gene MPV17 plays pleiotropic roles in mitochondria
Summary: The zebrafish mpv17−/− mutant shows a severe mitochondrial phenotype with ultrastructural alterations and oxidative phosphorylation impairment. The pyrimidine precursor orotic acid ameliorates mpv17−/− phenotype and increases mitochondrial DNA content, linking the loss of Mpv17 to pyrimidine de novo synthesis.
- Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain
Summary: Using a new reverse genetic screening method for zebrafish microglia development, involving automated image analysis, we identified that il34 facilitates yolk sac macrophage distribution to target organs, including the brain.
- Spotlight on zebrafish: the next wave of translational research
Summary: Zebrafish are a highly versatile and relevant organism for human disease modelling. This Editorial highlights the recent zebrafish research published in DMM.
- Leptin induces muscle wasting in a zebrafish kras-driven hepatocellular carcinoma (HCC) model
Summary: Through a zebrafish model, this study demonstrates that leptin plays an important role in cancer-induced muscle wasting and that the leptin pathway may be a therapeutic target in cancer cachexia.