A transgenic zebrafish model enabling controlled pancreatic β-cell ablation to simulate chronic hyperglycemia and study diabetes-related pathology.
This technology utilizes a highly active bacterial nitroreductase enzyme (NTR2.0) expressed specifically in zebrafish insulin-producing β-cells via a transgene, allowing selective ablation of these cells upon treatment with low doses of the antibiotic metronidazole (MTZ). This targeted β-cell destruction halts insulin production, inducing sustained elevated blood glucose levels that mimic human diabetic conditions. The model avoids toxic side effects typical of previous methods by requiring significantly lower MTZ doses, enabling chronic hyperglycemia studies and screening for treatments of diabetes-associated tissue damage.