Open AccessCombining streptozotocin and unilateral nephrectomy is an effective method for inducing experimental diabetic nephropathy in the ‘resistant’ C57Bl/6J mouse strain
Author(s) -
Melissa Uil,
Angelique M. L. Scantlebery,
Loes M. Butter,
Per Larsen,
Onno J. de Boer,
Jaklien C. Leemans,
Sandrine Florquin,
Joris J. T. H. Roelofs
Publication year - 2018
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-018-23839-9
Subject(s) - streptozotocin , diabetic nephropathy , albuminuria , medicine , endocrinology , diabetes mellitus , nephrectomy , glomerular basement membrane , type 2 diabetes , kidney , proteinuria
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.