Chair of Livestock Biotechnology, School of Life Sciences, Technische Universität München, 85354 Freising, Germany.
Chair of Livestock Biotechnology, School of Life Sciences, Technische Universität München, 85354 Freising, Germany
Dis Model Mech. 2018 Jan 22;11(1):dmm030783. doi: 10.1242/dmm.030783.
Genetically modified animals are vital for gaining a proper understanding of disease mechanisms. Mice have long been the mainstay of basic research into a wide variety of diseases but are not always the most suitable means of translating basic knowledge into clinical application. The shortcomings of rodent preclinical studies are widely recognised, and regulatory agencies around the world now require preclinical trial data from nonrodent species. Pigs are well suited to biomedical research, sharing many similarities with humans, including body size, anatomical features, physiology and pathophysiology, and they already play an important role in translational studies. This role is set to increase as advanced genetic techniques simplify the generation of pigs with precisely tailored modifications designed to replicate lesions responsible for human disease. This article provides an overview of the most promising and clinically relevant genetically modified porcine models of human disease for translational biomedical research, including cardiovascular diseases, cancers, diabetes mellitus, Alzheimer's disease, cystic fibrosis and Duchenne muscular dystrophy. We briefly summarise the technologies involved and consider the future impact of recent technical advances.
转基因动物对于深入了解疾病机制至关重要。长期以来，小鼠一直是各种疾病基础研究的主要工具，但它们并不总是将基础知识转化为临床应用的最适宜手段。啮齿动物临床前研究的局限性已得到广泛认可，世界各地的监管机构现在要求提供非啮齿动物物种的临床前试验数据。猪非常适合进行生物医学研究，它们与人有许多相似之处，包括体型、解剖特征、生理学和病理生理学，它们已经在转化研究中发挥了重要作用。随着先进的遗传技术的发展，能够更轻松地生成具有精确修饰的猪，以模拟导致人类疾病的病变，这种作用将会进一步增强。本文概述了用于转化医学研究的最有前途和最具临床相关性的人类疾病转基因猪模型，包括心血管疾病、癌症、糖尿病、阿尔茨海默病、囊性纤维化和杜氏肌营养不良症。我们简要总结了所涉及的技术，并考虑了最近技术进步的未来影响。
