The Jackson Laboratory, Bar Harbor, Maine 04609.
MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California, Davis School of Medicine, Sacramento, California 95817; email:
Annu Rev Anim Biosci. 2017 Feb 8;5:371-389. doi: 10.1146/annurev-animal-022516-022754.
Animal models offer heuristic research tools to understand the causes of human diseases and to identify potential treatments. With rapidly evolving genetic engineering technologies, mutations identified in a human disorder can be generated in the mouse genome. Phenotypic outcomes of the mutation are then explicated to confirm hypotheses about causes and to discover effective therapeutics. Most neurodevelopmental, neurodegenerative, and psychiatric disorders are diagnosed primarily by their prominent behavioral symptoms. Mouse behavioral assays analogous to the human symptoms have been developed to analyze the consequences of mutations and to evaluate proposed therapeutics preclinically. Here we describe the range of mouse behavioral tests available in the established behavioral neuroscience literature, along with examples of their translational applications. Concepts presented have been successfully used in other species, including flies, worms, fish, rats, pigs, and nonhuman primates. Identical strategies can be employed to test hypotheses about environmental causes and gene × environment interactions.
动物模型为理解人类疾病的病因和寻找潜在治疗方法提供了有益的研究工具。随着基因工程技术的快速发展,人类疾病中发现的突变可以在小鼠基因组中产生。然后对突变的表型结果进行阐述,以验证病因假说并发现有效的治疗方法。大多数神经发育、神经退行性和精神疾病主要根据其明显的行为症状进行诊断。已经开发出与人类症状类似的小鼠行为测定法,以分析突变的后果,并在临床前评估拟议的治疗方法。在这里,我们描述了已在既定行为神经科学文献中可用的一系列小鼠行为测试方法,并举例说明了它们的转化应用。所提出的概念已在包括苍蝇、蠕虫、鱼类、大鼠、猪和非人灵长类动物在内的其他物种中成功应用。相同的策略可以用于测试关于环境原因和基因×环境相互作用的假说。