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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.<\/jats:p>","DOI":"10.1038\/s41598-018-23839-9","type":"journal-article","created":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T22:23:43Z","timestamp":1522275823000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Combining streptozotocin and unilateral nephrectomy is an effective method for inducing experimental diabetic nephropathy in the \u2018resistant\u2019 C57Bl\/6J mouse strain"],"prefix":"10.1038","volume":"8","author":[{"given":"Melissa","family":"Uil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique M. 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