Young NOD mice show increased diabetes sensitivity to low doses of streptozotocin
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Updated: Jul 18, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Shiva Reddy1, Mike Chang, Elizabeth Robinson
1School of Biological Sciences, University of Auckland, Auckland, New Zealand. s.reddy@auckland.ac.nz
Abstract:
In type 1 diabetes, environmentally induced early-limited beta cell damage may pre-empt the subsequent immune-mediated beta cell destruction. Low doses of streptozotocin (Stz), given early to diabetes-prone mice, may cause limited beta cell destruction during the early phase and precipitate diabetes. Here, we aimed to see if young NOD mice are more diabetes-sensitive to various multiple low doses of Stz than non-diabetes-prone mice. We also determined the molecular pathology of islets following administration of the diabetogen. Female NOD and CD-1 mice received 5 daily doses of Stz at day 21 (20, 30, and 40 mg/kg body weight; 18 mice per group) or diluent, and diabetes was monitored. Pancreas were studied histochemically and immunohistochemically at various time points after Stz administration. Following administration of Stz, NOD mice showed a much earlier onset and increased diabetes rate, at all three doses, than CD-1 mice. By day 80, the final diabetes rates following the 40, 30, and 20 mg dose in NOD mice were 95%, 85%, and 33%, respectively, compared with 33%, 28%, and 5.5%, respectively, in CD-1 mice. However, following the 20 mg dose, only 2 of the 12 remaining NOD mice developed the disease between 90 and 250 days compared with 19 of 24 NOD mice that did not receive Stz at day 21. Stz-administered NOD and CD-1 mice showed an initial loss of beta cells, with redistribution of islet endocrine cells, early macrophage infiltration, and increasing insulitis.
Insights
Young NOD mice are more susceptible to streptozotocin (Stz)-induced diabetes than CD-1 mice. Early low-dose Stz administration accelerates diabetes onset and increases incidence in NOD mice, mimicking type 1 diabetes progression.
Area of Science:
- Immunology
- Endocrinology
- Diabetes Research
Background:
- Type 1 diabetes involves immune-mediated beta cell destruction.
- Early environmental factors may trigger beta cell damage, preceding immune attack.
- Streptozotocin (Stz) can induce diabetes in animal models.
Purpose of the Study:
- To assess the diabetes sensitivity of young NOD mice to multiple low doses of Stz compared to non-diabetes-prone mice.
- To investigate the molecular pathology of islets after Stz administration in NOD mice.
Main Methods:
- Female NOD and CD-1 mice received daily low doses of Stz (20, 30, 40 mg/kg) starting at day 21.
- Diabetes incidence and onset were monitored.
- Pancreatic islets were analyzed histochemically and immunohistochemically.
Main Results:
- NOD mice exhibited significantly earlier onset and higher diabetes rates across all Stz doses compared to CD-1 mice.
- At day 80, diabetes rates in NOD mice were 95% (40 mg/kg), 85% (30 mg/kg), and 33% (20 mg/kg), versus 33%, 28%, and 5.5% in CD-1 mice, respectively.
- Stz-treated NOD and CD-1 mice showed beta cell loss, islet endocrine cell redistribution, early macrophage infiltration, and increased insulitis.
Conclusions:
- Young NOD mice are highly sensitive to low-dose Stz, developing diabetes more readily than CD-1 mice.
- Early Stz administration in NOD mice accelerates diabetes development and alters islet pathology, providing a model for type 1 diabetes research.
- The findings suggest that early beta cell damage can precipitate autoimmune diabetes in susceptible individuals.
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