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转基因啮齿动物生产设施中的 3R 措施。

3R measures in facilities for the production of genetically modified rodents.

机构信息

Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

in vivo Research Facility, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

出版信息

Lab Anim (NY). 2022 Jun;51(6):162-177. doi: 10.1038/s41684-022-00978-1. Epub 2022 May 31.

DOI:10.1038/s41684-022-00978-1
PMID:35641635
Abstract

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.

摘要

人类与动物关系的社会文化变化导致了对生物医学研究中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:尽可能用替代方法代替动物实验,将使用的动物数量减少到科学合理的最低限度,并改进程序以最大限度地减少动物伤害。基因修饰有感知能力的动物(如老鼠)的产生涉及许多步骤,包括各种形式的操作。到目前为止,还没有对 3R 在基因操作中的应用进行综合分析。在这里,我们提供德国实验动物科学学会遗传学和繁殖委员会的指导方针,以在基因改造动物的产生过程中的每一步实施 3R。我们提供了应用 3R 的建议,以及从实验规划到技术选择、利害关系分析、饲养条件、基因改造系的管理和实际程序等每一步的成功/干预参数。我们还讨论了在发展技术的背景下动物福利的未来挑战。总的来说,我们希望我们的综合分析和对 3R 在啮齿动物基因修饰技术中适当实施的建议将使来自广泛学科的科学家受益,并有助于改善全球大量实验动物的福利。

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