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ILAR: A Retrospective and Prospective Look ILAR:回顾与展望
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2022-12-12 DOI: 10.1093/ilar/ilac018
R. Dysko, B. Natterson-Horowitz
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引用次数: 0
A Structured Approach to Optimizing Animal Model Selection for Human Translation: The Animal Model Quality Assessment. 优化人类翻译动物模型选择的结构化方法:动物模型质量评估。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2022-04-14 DOI: 10.1093/ilar/ilac004
Joanne Storey, T. Gobbetti, Alan R. Olzinski, B. Berridge
Animal studies in pharmaceutical drug discovery are common in preclinical research for compound evaluation before progression into human clinical trials. However, high rates of drug development attrition have prompted concerns regarding animal models and their predictive translatability to the clinic. To improve the characterization and evaluation of animal models for their translational relevance, the authors developed a tool to transparently reflect key features of a model that may be considered in both the application of the model but also the likelihood of successful translation of the outcomes to human patients. In this publication, we describe the rationale for the development of the Animal Model Quality Assessment tool, the questions used for the animal model assessment, and a high-level scoring system for the purpose of defining predictive translatability. Finally, we provide an example of a completed Animal Model Quality Assessment for the adoptive T-cell transfer model of colitis as a mouse model to mimic inflammatory bowel disease in humans.
药物发现的动物研究在临床前研究中很常见,用于化合物评估,然后进行人体临床试验。然而,药物开发的高损耗率引起了对动物模型及其对临床的预测可翻译性的关注。为了提高动物模型的翻译相关性的表征和评估,作者开发了一种工具,以透明地反映模型的关键特征,这些特征可能在模型的应用中被考虑,也可能成功地将结果翻译给人类患者。在本出版物中,我们描述了开发动物模型质量评估工具的基本原理,用于动物模型评估的问题,以及用于定义预测可翻译性的高级评分系统。最后,我们提供了一个完整的动物模型质量评估的例子,以过继性t细胞转移结肠炎模型作为模拟人类炎症性肠病的小鼠模型。
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引用次数: 4
Livestock and Risk Group 4 Pathogens: Researching Zoonotic Threats to Public Health and Agriculture in Maximum Containment. 牲畜和风险组4病原体:在最大限度的控制下研究人畜共患病对公共卫生和农业的威胁。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2022-01-07 DOI: 10.1093/ilar/ilab029
Charles E Lewis, Bradley Pickering

Maximum-containment laboratories are a unique and essential component of the bioeconomy of the United States. These facilities play a critical role in the national infrastructure, supporting research on a select set of especially dangerous pathogens, as well as novel, emerging diseases. Understanding the ecology, biology, and pathology at the human-animal interface of zoonotic spillover events is fundamental to efficient control and elimination of disease. The use of animals as human surrogate models or as target-host models in research is an integral part of unraveling the interrelated components involved in these dynamic systems. These models can prove vitally important in determining both viral- and host-factors associated with virus transmission, providing invaluable information that can be developed into better risk mitigation strategies. In this article, we focus on the use of livestock in maximum-containment, biosafety level-4 agriculture (BSL-4Ag) research involving zoonotic, risk group 4 pathogens and we provide an overview of historical associated research and contributions. Livestock are most commonly used as target-host models in high-consequence, maximum-containment research and are routinely used to establish data to assist in risk assessments. This article highlights the importance of animal use, insights gained, and how this type of research is essential for protecting animal health, food security, and the agriculture economy, as well as human public health in the face of emerging zoonotic pathogens. The utilization of animal models in high-consequence pathogen research and continued expansion to include available species of agricultural importance is essential to deciphering the ecology of emerging and re-emerging infectious diseases, as well as for emergency response and mitigation preparedness.

最大密闭实验室是美国生物经济的一个独特而重要的组成部分。这些设施在国家基础设施中发挥着关键作用,支持对一系列特别危险的病原体以及新出现的疾病进行研究。了解人畜共患溢出事件的人-动物界面的生态学、生物学和病理学是有效控制和消除疾病的基础。在研究中使用动物作为人类替代模型或作为目标宿主模型是揭示这些动态系统中涉及的相互关联的组成部分的一个组成部分。这些模型对于确定与病毒传播相关的病毒和宿主因素至关重要,提供了宝贵的信息,可用于制定更好的风险缓解战略。在这篇文章中,我们关注的是在最大限度控制、生物安全4级农业(BSL-4Ag)中使用牲畜的研究,涉及人畜共患病、风险组4的病原体,我们提供了历史相关研究和贡献的概述。在高后果、最大限度遏制研究中,牲畜最常被用作目标宿主模型,并经常用于建立数据以协助风险评估。本文强调了动物使用的重要性,获得的见解,以及这类研究如何在面对新出现的人畜共患病原体时对保护动物健康、食品安全和农业经济以及人类公共卫生至关重要。在后果严重的病原体研究中利用动物模型,并继续扩大以包括具有农业重要性的现有物种,对于破译新出现和再出现的传染病的生态学,以及对紧急情况的反应和减灾准备至关重要。
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引用次数: 4
Animals as Beneficiaries of Biomedical Research Originally Intended for Humans. 动物作为最初用于人类的生物医学研究的受益者。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilac014
Franklin M Loew
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引用次数: 0
ICLAS LAQ Network for the Promotion of Animal Quality in Research. 促进研究动物质量的LAQ网络。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilac003
Patri Vergara, Gregory Ballard, Cynthia Besch-Williford, Nobuhito Hayashimoto, Cynthia Pekow, Ana Perez, Katja Schmidt, William Shek, Martin Toft, Atsushi Yoshiki

ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Evaluation Program (PEP), which focuses on microbial monitoring by and for laboratory animal diagnostic laboratories, and the Genetic Reference Monitoring Program (GENRef), which provides assay-ready reference DNA for genetic testing of mouse strains. Since 2008, PEP has grown to become a truly international program with participating laboratories in 5 continents. Launched in 2016, GENRef currently distributes DNA from 12 common inbred mouse strains for use in genetic monitoring of locally inbred colonies as well as for genetic testing of stocks, particularly genetically engineered stocks, of uncertain origins. GENRef has the capacity to include additional strains as well as additional species. PEP and GENRef provide the reagents at cost, as a resource to the international scientific community, in the interest of improving research quality in an environment of growing concern for research quality, rigor, and reproducibility.

ICLAS实验动物质量网络(LAQN)项目目前由性能评估项目(PEP)和遗传参考监测项目(GENRef)组成,前者侧重于实验室动物诊断实验室的微生物监测,后者为小鼠品系的基因检测提供可检测的参考DNA。自2008年以来,PEP已发展成为一个真正的国际项目,参与实验室遍布五大洲。GENRef于2016年启动,目前分发来自12种常见近亲繁殖小鼠品系的DNA,用于对当地近亲繁殖菌落进行遗传监测,以及对来源不确定的基因工程种群进行基因检测。GENRef有能力包括额外的菌株和额外的物种。PEP和GENRef以成本价提供试剂,作为国际科学界的资源,在日益关注研究质量、严谨性和可重复性的环境中提高研究质量。
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引用次数: 0
Erratum to: "But Mouse, You Are Not Alone": On Some Severe Acute Respiratory Syndrome Coronavirus 2 Variants Infecting Mice. “但是老鼠,你并不孤单”:关于一些感染老鼠的严重急性呼吸综合征冠状病毒2变异。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilac002
Michael J Kuiper, Laurence O W Wilson, Shruthi Mangalaganesh, Carol Lee, Daniel Reti, Seshadri S Vasan
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引用次数: 1
Type I Hypersensitivity in Ferrets Following Exposure to SARS-CoV-2 Inoculum: Lessons Learned. 雪貂接触SARS-CoV-2接种后的I型超敏反应:经验教训
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilab019
Daniel Layton, Kathie Burkett, Glenn A Marsh, Nagendrakumar B Singanallur, Jennifer Barr, Rachel Layton, Sarah-Jane Riddell, Sheree Brown, Lee Trinidad, Gough G Au, Alexander J McAuley, Suzanne Lowther, James Watson, Seshadri S Vasan

This case report discusses Type I hypersensitivity in ferrets following exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inoculum, observed during a study investigating the efficacy of candidate COVID-19 vaccines. Following a comprehensive internal root-cause investigation, it was hypothesized that prior prime-boost immunization of ferrets with a commercial canine C3 vaccine to protect against the canine distemper virus had resulted in primary immune response to fetal bovine serum (FBS) in the C3 preparation. Upon intranasal exposure to SARS-CoV-2 virus cultured in medium containing FBS, an allergic airway response occurred in 6 out of 56 of the ferrets. The 6 impacted ferrets were randomly dispersed across study groups, including different COVID-19 vaccine candidates, routes of vaccine candidate administration, and controls (placebo). The root-cause investigation and subsequent analysis determined that the allergic reaction was unrelated to the COVID-19 vaccine candidates under evaluation. Histological assessment suggested that the allergic response was characterized by eosinophilic airway disease; increased serum immunoglobulin levels reactive to FBS further suggested this response was caused by immune priming to FBS present in the C3 vaccine. This was further supported by in vivo studies demonstrating ferrets administered diluted FBS also presented clinical signs consistent with a hyperallergic response, while clinical signs were absent in ferrets that received a serum-free SARS-CoV-2 inoculum. It is therefore recommended that vaccine studies in higher order animals should consider the impact of welfare vaccination and use serum-free inoculum whenever possible.

本病例报告讨论了在一项调查候选COVID-19疫苗疗效的研究中观察到的雪貂在接触严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)接种后出现的I型超敏反应。在一项全面的内部根本原因调查后,假设先前用商用犬C3疫苗免疫雪貂以预防犬瘟热病毒,导致了对C3制剂中的胎牛血清(FBS)的初级免疫反应。经鼻接触在含有FBS的培养基中培养的SARS-CoV-2病毒后,56只雪貂中有6只发生了过敏性气道反应。6只受影响的雪貂随机分散在不同的COVID-19候选疫苗、候选疫苗给药途径和对照组(安慰剂)的研究组中。根本原因调查和随后的分析确定过敏反应与正在评估的COVID-19候选疫苗无关。组织学评价提示过敏性反应以嗜酸性气道疾病为特征;血清免疫球蛋白水平对FBS反应性升高进一步表明,这种反应是由C3疫苗中对FBS的免疫启动引起的。体内研究进一步支持了这一点,该研究表明,给予稀释FBS的雪貂也出现了与超过敏反应一致的临床症状,而接受无血清SARS-CoV-2接种的雪貂则没有临床症状。因此,建议在高等动物中进行的疫苗研究应考虑福利疫苗接种的影响,并尽可能使用无血清接种。
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引用次数: 1
A Brief History of Use of Animals in Biomedical Research and Perspective on Non-Animal Alternatives. 生物医学研究中动物使用简史及非动物替代品展望。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilab020
Lewis B Kinter, Ron DeHaven, David K Johnson, Joseph J DeGeorge

Animals have been closely observed by humans for at least 17 000 years to gain critical knowledge for human and later animal survival. Routine scientific observations of animals as human surrogates began in the late 19th century driven by increases in new compounds resulting from synthetic chemistry and requiring characterization for potential therapeutic utility and safety. Statistics collected by the United States Department of Agriculture's Animal and Plant Health Inspection Service and United Kingdom Home Office show that animal usage in biomedical research and teaching activities peaked after the mid-20th century and thereafter fell precipitously until the early 21st century, when annual increases (in the UK) were again observed, this time driven by expansion of genetically modified animal technologies. The statistics also show a dramatic transfer of research burden in the 20th and 21st centuries away from traditional larger and more publicly sensitive species (dogs, cats, non-human primates, etc) towards smaller, less publicly sensitive mice, rats, and fish. These data show that new technology can produce multi-faceted outcomes to reduce and/or to increase annual animal usage and to redistribute species burden in biomedical research. From these data, it is estimated that annual total vertebrate animal usage in biomedical research and teaching in the United States was 15 to 25 million per year during 2001-2018. Finally, whereas identification and incorporation of non-animal alternatives are products of, but not an integral component of, the animal research cycle, they replace further use of animals for specific research and product development purposes and create their own scientific research cycles, but are not necessarily a substitute for animals or humans for discovery, acquisition, and application of new (eg, previously unknown and/or unsuspected) knowledge critical to further advance human and veterinary medicine and global species survival.

人类对动物的密切观察至少有17000年,以获得人类和后来动物生存的关键知识。19世纪后期,由于合成化学产生的新化合物的增加以及对潜在治疗效用和安全性的要求,对动物作为人类替代品的常规科学观察开始了。美国农业部动植物卫生检验局和英国内政部收集的统计数据表明,生物医学研究和教学活动中动物的使用在20世纪中叶之后达到顶峰,此后急剧下降,直到21世纪初才再次出现年度增长(在英国),这一次是由转基因动物技术的扩张推动的。统计数据还显示,在20世纪和21世纪,研究负担从传统的体型较大、对公众敏感的物种(狗、猫、非人类灵长类动物等)急剧转移到体型较小、对公众敏感程度较低的小鼠、大鼠和鱼类。这些数据表明,新技术可以产生多方面的结果,以减少和/或增加每年的动物使用量,并重新分配生物医学研究中的物种负担。根据这些数据,据估计,2001年至2018年期间,美国生物医学研究和教学中每年使用的脊椎动物总数为1500万至2500万只。最后,虽然非动物替代品的识别和纳入是动物研究周期的产物,但不是动物研究周期的组成部分,它们取代了为特定研究和产品开发目的进一步使用动物,并创造了自己的科学研究周期,但不一定取代动物或人类发现、获取和应用新的(例如:以前未知和/或未怀疑的)知识对进一步推进人类和兽医医学以及全球物种生存至关重要。
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引用次数: 9
International Standardized Nomenclature for Outbred Stocks of Laboratory Animals. 实验动物近亲繁殖的国际标准化命名法。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilac013
M Festing, K Kondo, R Loosli, S M Poiley, A Spiegel

In accordance with the «Aims of ICLA» (ICLA Bulletin No. 26, March 1970) the Governing Board established in 1969 a Working Party to prepare an International Nomenclature System for Outbred Animals. The members were: Professor, Dr. A. Spiegel, Federal Republic of Germany, chairman.Dr. M. Festing, United KingdomDr. K. Kondo, JapanDr. R. Loosli, SwitzerlandMr. S. Poiley, U.S.A. The nomenclature rules, completed and approved by the ICLA Governing Board on 8 December 1971, are published herewith. I am convinced that this system will bring order out of the existing chaos. The system is an offer to the world laboratory animal science, particularly the breeders and users. Editors of scientific journals, catalogues, and indices all over the world are also encouraged to require and use animal stock identification by this system for outbred animals used in experimentation. The ICLA Governing Board would have preferred to have seen an international centralization of symbol registration. However, the ICLA Secretariat has not got the capacity necessary for such a task and some practical solution to the registration problem will have to be found by the Governing Board. A final aim should then be for ICLA to publish a comprehensive world list of breeder symbols at intervals. Oslo, January 1972 Stian Erichsen  Secretary-General.

根据“ICLA的目标”(ICLA公报第26号,1970年3月),理事会于1969年成立了一个工作组,以准备国际近亲繁殖动物命名系统。成员包括:教授,德意志联邦共和国A. Spiegel博士,主席。费斯汀先生,英国近藤,日本R. Loosli瑞士ICLA理事会于1971年12月8日完成并批准的命名规则现随信公布。我深信这一制度将使现存的混乱中恢复秩序。该系统是为世界实验动物科学,特别是育种者和用户提供的一项服务。还鼓励世界各地的科学期刊、目录和索引的编辑要求并使用该系统对用于实验的近亲繁殖动物进行动物种群鉴定。ICLA理事会本来希望看到符号注册的国际集中化。但是,国际法委员会秘书处还没有具备完成这项任务所必需的能力,理事会必须找到解决登记问题的一些实际办法。ICLA的最终目标应该是每隔一段时间发布一份全面的世界育种标志名录。1972年1月,奥斯陆斯蒂安·埃里克森秘书长。
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引用次数: 0
Rapid Response by Laboratory Animal Research Institutions During the COVID-19 Pandemic: Key Lessons Learned From a 2021 National Academies of Sciences, Engineering, and Medicine Workshop. 2019冠状病毒病大流行期间实验动物研究机构的快速反应:从2021年国家科学院、工程院和医学院研讨会上吸取的主要经验教训。
IF 2.5 3区 农林科学 Q1 VETERINARY SCIENCES Pub Date : 2021-12-31 DOI: 10.1093/ilar/ilac009
Jill Ascher, Joyce Cohen, Michael J Huerkamp, David M Kurtz, Joseph T Newsome, Brianna Skinner
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引用次数: 0
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