A new model of inducible chronic hyperglycemia.
Tori R TuckerCourtney A KnitterDeena M KhourySheida EshghiSophia TranAbigail V SharrockTravis J WilesDavid F AckerleyJeff S MummMichael J ParsonsPublished in: Disease models & mechanisms (2023)
Transgene driven expression of E. coli nitroreductase (NTR1.0) renders animal cells susceptible to the antibiotic metronidazole (MTZ). Many NTR1.0/MTZ ablation tools have been reported in the zebrafish that have significantly impacted regeneration studies. However, NTR1.0-based tools are not appropriate for modeling chronic cell loss as prolonged application of the required MTZ dose (10 mM) is deleterious to zebrafish health. We established this dose corresponds to the LD50 of MTZ in larval and adult zebrafish and that it induced intestinal pathology. NTR2.0 is a more active NTR engineered from Vibrio vulnificus NfsB that requires substantially less MTZ to induce cell ablation. Here we report on the generation of two new NTR2.0-based zebrafish lines where acute β-cell ablation can be achieved without MTZ-associated intestinal pathology. For the first time, we were able to sustain β-cell loss and maintain elevated glucose levels (chronic hyperglycemia) in larvae and adults. Adult fish showed significant weight loss consistent with the induction of a diabetic state, indicating this paradigm will allow the modeling of diabetes and associated pathologies.
Keyphrases
- single cell
- cell therapy
- type diabetes
- healthcare
- drug induced
- stem cells
- public health
- diabetic rats
- risk assessment
- induced apoptosis
- oxidative stress
- blood pressure
- pseudomonas aeruginosa
- staphylococcus aureus
- roux en y gastric bypass
- metabolic syndrome
- cystic fibrosis
- mesenchymal stem cells
- intensive care unit
- cell proliferation
- liver failure
- bone marrow
- young adults
- climate change
- binding protein
- endoplasmic reticulum stress
- high glucose
- catheter ablation
- health promotion