Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis

Q1 Agricultural and Biological Sciences Current protocols in mouse biology Pub Date : 2016-06-01 DOI:10.1002/cpmo.1

Jef Verbeek, Ans Jacobs, Pieter Spincemaille, David Cassiman

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引用次数: 9

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non–genetically manipulated C57BL6/J mice a ‘Western style’ high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc.

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非酒精性脂肪性肝炎小鼠模型的建立

非酒精性脂肪性肝病(NAFLD)是西方世界最常见的肝脏疾病。它代表了从孤立性脂肪变性到非酒精性脂肪性肝炎(NASH)的疾病谱系。特别是，NASH可发展为纤维化、肝硬化、肝细胞癌和肝功能衰竭。由于缺乏具有代表性的NASH小鼠模型，新的治疗策略的发展受到阻碍。在这里，我们描述了一种NASH小鼠模型，该模型基于给非基因操纵的C57BL6/J小鼠喂食“西式”高脂肪/高糖饮食(HF-HSD)。HF-HSD会导致早期肥胖、胰岛素抵抗和高胆固醇血症。经过12周的HF-HSD治疗后，所有小鼠都表现出NASH的全部特征，包括脂肪变性、肝细胞球囊化和小叶炎症，大多数小鼠还伴有纤维化。因此，这个模型与人类疾病非常相似。该小鼠模型的实施将为评估(i) NAFLD向NASH发展的潜在机制以及(ii) NASH的治疗干预措施带来标准化的设置。©2016 by John Wiley &儿子,Inc。

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Current protocols in mouse biology Agricultural and Biological Sciences-Animal Science and Zoology

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期刊介绍： Sound and reproducible laboratory methods are the foundation of scientific discovery. Yet, all too often, nuances that are critical for an experiment''s success are not captured in the primary literature but exist only as part of a lab''s oral tradition. The aim of Current Protocols in Mouse Biology is to provide the clearest, most detailed and reliable step-by-step instructions for protocols involving the use of mice in biomedical research. Written by experts in the field and extensively edited to our exacting standards, the protocols include all of the information necessary to complete an experiment in the laboratory—introduction, materials lists with supplier information, detailed step-by-step procedures with helpful annotations, recipes for reagents and solutions, illustrative figures and information-packed tables. Each article also provides invaluable discussions of background information, applications of the methods, important assumptions, key parameters, time considerations, and tips to help avoid common pitfalls and troubleshoot experiments. Furthermore, Current Protocols in Mouse Biology content is thoughtfully organized by topic for optimal usage and to maximize contextual knowledge. Quarterly issues allow Current Protocols to constantly evolve to keep pace with the newest discoveries and developments. Current Protocols in Mouse Biology brings together resources in mouse biology and genetics and provides a mouse protocol resource that covers all aspects of mouse biology. Current Protocols in Mouse Biology also permits optimization of mouse model usage, which is significantly impacted by both cost and ethical constraints. Optimal and standardized mouse protocols ultimately reduce experimental variability and reduce the number of animals used in mouse experiments.