Polejaeva Irina A, Rutigliano Heloisa M, Wells Kevin D
Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT 84322, USA.
Division of Animal Sciences, Animal Sciences Research Center, University of Missouri, Columbia, MO 65211, USA.
Reprod Fertil Dev. 2016;28(1-2):112-24. doi: 10.1071/RD15343.
Livestock models have contributed significantly to biomedical and surgical advances. Their contribution is particularly prominent in the areas of physiology and assisted reproductive technologies, including understanding developmental processes and disorders, from ancient to modern times. Over the past 25 years, biomedical research that traditionally embraced a diverse species approach shifted to a small number of model species (e.g. mice and rats). The initial reasons for focusing the main efforts on the mouse were the availability of murine embryonic stem cells (ESCs) and genome sequence data. This powerful combination allowed for precise manipulation of the mouse genome (knockouts, knockins, transcriptional switches etc.) leading to ground-breaking discoveries on gene functions and regulation, and their role in health and disease. Despite the enormous contribution to biomedical research, mouse models have some major limitations. Their substantial differences compared with humans in body and organ size, lifespan and inbreeding result in pronounced metabolic, physiological and behavioural differences. Comparative studies of strategically chosen domestic species can complement mouse research and yield more rigorous findings. Because genome sequence and gene manipulation tools are now available for farm animals (cattle, pigs, sheep and goats), a larger number of livestock genetically engineered (GE) models will be accessible for biomedical research. This paper discusses the use of cattle, goats, sheep and pigs in biomedical research, provides an overview of transgenic technology in farm animals and highlights some of the beneficial characteristics of large animal models of human disease compared with the mouse. In addition, status and origin of current regulation of GE biomedical models is also reviewed.
家畜模型对生物医学和外科手术的进展做出了重大贡献。从古至今，它们在生理学和辅助生殖技术领域的贡献尤为突出，包括对发育过程和疾病的理解。在过去25年里，传统上采用多种物种方法的生物医学研究转向了少数几种模式物种（如小鼠和大鼠）。将主要精力集中在小鼠上的最初原因是小鼠胚胎干细胞（ESC）的可用性和基因组序列数据。这种强大的组合使得对小鼠基因组进行精确操作（基因敲除、基因敲入、转录开关等）成为可能，从而在基因功能和调控及其在健康和疾病中的作用方面取得了开创性的发现。尽管对生物医学研究做出了巨大贡献，但小鼠模型存在一些重大局限性。它们在身体和器官大小、寿命和近亲繁殖方面与人类存在显著差异，导致明显的代谢、生理和行为差异。对经过战略选择的家养物种进行比较研究可以补充小鼠研究，并得出更严谨的结果。由于现在已有家畜（牛、猪、绵羊和山羊）的基因组序列和基因操作工具，将有更多的家畜基因工程（GE）模型可用于生物医学研究。本文讨论了牛、山羊、绵羊和猪在生物医学研究中的应用，概述了家畜转基因技术，并强调了与小鼠相比人类疾病大型动物模型的一些有益特征。此外，还综述了当前基因工程生物医学模型监管的现状和起源。
