Sociocultural changes in the human–animal relationship have led to increasing demands for animal welfare in biomedical research. The 3R concept is the basis for bringing this demand into practice: Replace animal experiments with alternatives where possible, Reduce the number of animals used to a scientifically justified minimum and Refine the procedure to minimize animal harm. The generation of gene-modified sentient animals such as mice and rats involves many steps that include various forms of manipulation. So far, no coherent analysis of the application of the 3Rs to gene manipulation has been performed. Here we provide guidelines from the Committee on Genetics and Breeding of Laboratory Animals of the German Society for Laboratory Animal Science to implement the 3Rs in every step during the generation of genetically modified animals. We provide recommendations for applying the 3Rs as well as success/intervention parameters for each step of the process, from experiment planning to choice of technology, harm–benefit analysis, husbandry conditions, management of genetically modified lines and actual procedures. We also discuss future challenges for animal welfare in the context of developing technologies. Taken together, we expect that our comprehensive analysis and our recommendations for the appropriate implementation of the 3Rs to technologies for genetic modifications of rodents will benefit scientists from a wide range of disciplines and will help to improve the welfare of a large number of laboratory animals worldwide.

人与动物关系的社会文化变化导致生物医​​学研究对动物福利的需求不断增加。3R 概念是将这一需求付诸实践的基础：在可能的情况下用替代品代替动物实验，将使用的动物数量减少到科学合理的最低限度，并改进减少动物伤害的程序。基因修饰的有知觉动物（例如小鼠和大鼠）的产生涉及许多步骤，其中包括各种形式的操作。到目前为止，还没有对 3Rs 在基因操作中的应用进行连贯的分析。在这里，我们提供了德国实验动物科学学会实验动物遗传学和育种委员会的指导方针，以在转基因动物产生过程中的每一步实施 3R。我们为流程的每个步骤应用 3R 以及成功/干预参数提供建议，从实验计划到技术选择、危害-效益分析、饲养条件、转基因品系的管理和实际程序。我们还在开发技术的背景下讨论了动物福利的未来挑战。总而言之，我们希望我们的全面分析和我们对适当实施啮齿动物基因修饰技术 3R 的建议将造福于广泛学科的科学家，并将有助于改善全球大量实验动物的福利.