Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A barrier to progress in these areas has been a lack of animal models that faithfully replicate the main features of human DN. Such models could be used to define the pathogenesis, identify drug targets and test new therapies. Owing to their tractability for genetic manipulation, mice are widely used to model human diseases, including DN. Questions have been raised, however, about the general utility of mouse models in human drug discovery. Standard mouse models of diabetes typically manifest only modest kidney abnormalities, whereas accelerated models, induced by superimposing genetic stressors, recapitulate key features of human DN. Incorporation of systems biology approaches and emerging data from genomics and metabolomics studies should enable further model refinement. Here, we discuss the current status of mouse models for DN, their limitations and opportunities for improvement. We emphasize that future efforts should focus on generating robust models that reproduce the major clinical and molecular phenotypes of human DN.

在发达国家，糖尿病肾病（DN）是终末期肾脏疾病的主要原因。因此，迫切需要新的治疗方法以及生物标记物，以对糖尿病个体中DN的风险进行分层。在这些领域取得进展的障碍是缺乏能忠实复制人类DN的主要特征的动物模型。此类模型可用于定义发病机制，确定药物靶标并测试新疗法。由于其易于遗传操作，因此小鼠被广泛用于模拟包括DN在内的人类疾病。然而，已经提出了关于小鼠模型在人类药物发现中的一般用途的问题。糖尿病的标准小鼠模型通常仅表现出中等程度的肾脏异常，而通过叠加遗传应激因素诱导的加速模型，概括了人类DN的关键特征。结合系统生物学方法和来自基因组学和代谢组学研究的新兴数据，应能进一步完善模型。在这里，我们讨论了DN鼠标模型的当前状态，它们的局限性和改进的机会。我们强调，未来的工作应集中在生成可重现人类DN主要临床和分子表型的可靠模型上。