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Combining streptozotocin and unilateral nephrectomy is an effective method for inducing experimental diabetic
Melissa Uil1, Angelique M L Scantlebery1, Loes M Butter1
1Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Abstract:
Diabetic nephropathy (DN) is the leading cause of chronic kidney disease. Animal models are essential tools for designing new strategies to prevent DN. C57Bl/6 (B6) mice are widely used for transgenic mouse models, but are relatively resistant to DN. This study aims to identify the most effective method to induce DN in a type 1 (T1D) and a type 2 diabetes (T2D) model in B6 mice. For T1D-induced DN, mice were fed a control diet, and randomised to streptozotocin (STZ) alone, STZ+unilateral nephrectomy (UNx), or vehicle/sham. For T2D-induced DN, mice were fed a western (high fat) diet, and randomised to either STZ alone, STZ+UNx, UNx alone, or vehicle/sham. Mice subjected to a control diet with STZ +UNx developed albuminuria, glomerular lesions, thickening of the glomerular basement membrane, and tubular injury. Mice on control diet and STZ developed only mild renal lesions. Furthermore, kidneys from mice on a western diet were hardly affected by diabetes, UNx or the combination. We conclude that STZ combined with UNx is the most effective model to induce T1D-induced DN in B6 mice. In our hands, combining western diet and STZ treatment with or without UNx did not result in a T2D-induced DN model in B6 mice.
Insights
The most effective method to induce diabetic nephropathy (DN) in C57Bl/6 mice involves streptozotocin (STZ) combined with unilateral nephrectomy (UNx). This approach successfully models type 1 diabetes-induced DN, but not type 2 diabetes-induced DN.
Area of Science:
- Nephrology
- Endocrinology
- Animal Models
Background:
- Diabetic nephropathy (DN) is a primary cause of chronic kidney disease.
- C57Bl/6 (B6) mice are valuable for research but are relatively resistant to DN.
- Effective animal models are crucial for developing DN prevention strategies.
Purpose of the Study:
- To determine the optimal method for inducing DN in type 1 (T1D) and type 2 diabetes (T2D) models using B6 mice.
- To evaluate the efficacy of streptozotocin (STZ) and unilateral nephrectomy (UNx) in B6 mouse models.
Main Methods:
- For T1D: B6 mice received a control diet and were randomized to STZ alone, STZ+UNx, or vehicle/sham.
- For T2D: B6 mice received a western diet and were randomized to STZ alone, STZ+UNx, UNx alone, or vehicle/sham.
Main Results:
- STZ combined with UNx in mice on a control diet induced significant albuminuria, glomerular lesions, thickened glomerular basement membranes, and tubular injury.
- STZ alone on a control diet resulted in only mild renal lesions.
- A western diet, with or without STZ and/or UNx, did not effectively induce DN in B6 mice.
Conclusions:
- Streptozotocin (STZ) plus unilateral nephrectomy (UNx) is the most effective method for inducing type 1 diabetes-induced diabetic nephropathy (DN) in C57Bl/6 mice.
- The combination of a western diet with STZ and/or UNx did not establish a reliable model for type 2 diabetes-induced DN in B6 mice.