Combining streptozotocin and unilateral nephrectomy is an effective method for inducing experimental diabetic nephropathy in the ‘resistant’ C57Bl/6J mouse strain

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 me...

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Bibliographic Details
Published in:Scientific reports Vol. 8; no. 1; pp. 5542 - 10
Main Authors: Uil, Melissa, Scantlebery, Angelique M. L., Butter, Loes M., Larsen, Per W. B., de Boer, Onno J., Leemans, Jaklien C., Florquin, Sandrine, Roelofs, Joris J. T. H.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 03.04.2018
Nature Publishing Group
Nature Portfolio
Subjects:
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Animal diseases
Animal models
Animals
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Experimental - chemically induced
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - surgery
Diabetes Mellitus, Type 1 - chemically induced
Diabetes Mellitus, Type 1 - complications
Diabetes Mellitus, Type 1 - surgery
Diabetic Nephropathies - etiology
Diabetic Nephropathies - pathology
Diabetic nephropathy
Diet
Disease Models, Animal
High fat diet
Humanities and Social Sciences
Kidneys
Lesions
Male
Mice
Mice, Inbred C57BL
multidisciplinary
Nephrectomy
Nephrectomy - adverse effects
Nephropathy
Rodents
Science
Science (multidisciplinary)
Streptozocin
Streptozocin - toxicity
Transgenic mice
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-23839-9