 Subjects -> VETERINARY SCIENCE (Total: 220 journals)
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- Animal Study Translation: The Other Reproducibility Challenge
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Authors: Berridge B.
Pages: 1 - 6
Abstract: Animal research is currently an irreplaceable contributor to our efforts to protect and improve public health. Its relevance, importance, and contributions are represented in historical precedent, regulatory expectations, evidence of our rapidly developing understanding of human health and disease, as well as success in the development of novel therapeutics that are improving quality of life and extending human and animal life expectancy. The rapid and evolving success in responding to the current COVID pandemic significantly supported by animal studies is a clear example of the importance of animal research. But there is growing interest in reducing our dependence on animals and challenges to the effective translation of current animal studies to human applications. There are several potential contributors to gaps in the translatability of animal research to humans, including our approaches to choosing or rationalizing the relevance of a particular animal model, our understanding of their biological variability and how that applies to outcomes, the data we collect from animal studies, and even how we manage the animals. These important contributors to the success of animal research are explored in this issue of the ILAR Journal.
PubDate: Thu, 14 Apr 2022 00:00:00 GMT
DOI: 10.1093/ilar/ilac005
Issue No: Vol. 62, No. 1-2 (2022)
- “But Mouse, You Are Not Alone”: On Some Severe Acute Respiratory
Syndrome Coronavirus 2 Variants Infecting Mice-
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Authors: Kuiper M; Wilson L, Mangalaganesh S, et al.
Pages: 48 - 59
Abstract: In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein’s receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K, and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface, are, however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date. Our current understanding thus points to the Alpha, Beta, Gamma, and Omicron variants of concern infecting mice, whereas Delta and “Delta Plus” lack a similar biomolecular basis to do so. This paper identifies 11 countries (Brazil, Chile, Djibouti, Haiti, Malawi, Mozambique, Reunion, Suriname, Trinidad and Tobago, Uruguay, and Venezuela) where targeted local field surveillance of mice is encouraged because they may have come in contact with humans who had the virus with adaptive mutation(s). It also provides a systematic methodology to analyze the potential for other animal reservoirs and their likely locations.
PubDate: Wed, 12 Jan 2022 00:00:00 GMT
DOI: 10.1093/ilar/ilab031
Issue No: Vol. 62, No. 1-2 (2022)
- A Structured Approach to Optimizing Animal Model Selection for Human
Translation: The Animal Model Quality Assessment-
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Authors: Storey J; Gobbetti T, Olzinski A, et al.
Pages: 66 - 76
Abstract: 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.
PubDate: Thu, 14 Apr 2022 00:00:00 GMT
DOI: 10.1093/ilar/ilac004
Issue No: Vol. 62, No. 1-2 (2022)
- Research-Relevant Conditions and Pathology of Laboratory Mice, Rats,
Gerbils, Guinea Pigs, Hamsters, Naked Mole Rats, and Rabbits-
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Authors: Cooper T; Meyerholz D, Beck A, et al.
Pages: 77 - 132
Abstract: Animals are valuable resources in biomedical research in investigations of biological processes, disease pathogenesis, therapeutic interventions, safety, toxicity, and carcinogenicity. Interpretation of data from animals requires knowledge not only of the processes or diseases (pathophysiology) under study but also recognition of spontaneous conditions and background lesions (pathology) that can influence or confound the study results. Species, strain/stock, sex, age, anatomy, physiology, spontaneous diseases (noninfectious and infectious), and neoplasia impact experimental results and interpretation as well as animal welfare. This review and the references selected aim to provide a pathology resource for researchers, pathologists, and veterinary personnel who strive to achieve research rigor and validity and must understand the spectrum of “normal” and expected conditions to accurately identify research-relevant experimental phenotypes as well as unusual illness, pathology, or other conditions that can compromise studies involving laboratory mice, rats, gerbils, guinea pigs, hamsters, naked mole rats, and rabbits.
PubDate: Tue, 04 Jan 2022 00:00:00 GMT
DOI: 10.1093/ilar/ilab022
Issue No: Vol. 62, No. 1-2 (2022)
- Erratum to: “But Mouse, You Are Not Alone”: On Some Severe Acute
Respiratory Syndrome Coronavirus 2 Variants Infecting Mice-
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Authors: Kuiper M; Wilson L, Mangalaganesh S, et al.
Pages: 274 - 274
Abstract: In the originally published version of this manuscript, the article received date was listed as October 31, 2021 in error. The correct article history is as follows: “Received: August 4, 2021. Revised: October 31, 2021. Accepted: November 21, 2021.” This error has been corrected.
PubDate: Wed, 23 Feb 2022 00:00:00 GMT
DOI: 10.1093/ilar/ilac002
Issue No: Vol. 62, No. 1-2 (2022)
- A Brief History of Use of Animals in Biomedical Research and Perspective
on Non-Animal Alternatives-
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Authors: Kinter L; DeHaven R, Johnson D, et al.
Pages: 7 - 16
Abstract: 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.
PubDate: Fri, 25 Jun 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab020
Issue No: Vol. 62, No. 1-2 (2021)
- Animal Models of COVID-19 II. Comparative Immunology
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Authors: Veenhuis R; Zeiss C.
Pages: 17 - 34
Abstract: Developing strong animal models is essential for furthering our understanding of how the immune system functions in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The alarming speed at which SARS-CoV-2 has spread, and the high mortality rate of severe Coronavirus Disease 2019 (COVID-19), has required both basic science and clinical research to move at an unprecedented pace. Models previously developed to study the immune response against SARS-CoV have been rapidly deployed to now study SARS-CoV-2. To date, both small and large animal models are remarkably consistent when infected with SARS-CoV-2; however, certain models have proven more useful when answering specific immunological questions than others. Small animal models, such as Syrian hamsters, ferrets, and mice carrying the hACE2 transgene, appear to reliably recapitulate the initial cytokine surge seen in COVID-19 as well as show significant innate and adaptive cell infiltration in to the lung early in infection. Additionally, these models develop strong antibody responses to the virus, are protected from reinfection, and genetically modified versions exist that can be used to ask specific immunological questions. Large animal models such as rhesus and cynomologus macaques and African green monkeys are critical to understanding how the immune system responds to SARS-CoV-2 infection because they are considered to be the most similar to humans. These models are considered the gold standard for assessing vaccine efficacy and protection, and recapitulate the initial cytokine surge, immune cell infiltration into the lung, certain aspects of thrombosis, and the antibody and T-cell response to the virus. In this review, we discuss both small and large animal model studies previously used in SARS-CoV-2 research that may be useful in elucidating the immunological contributions to hallmark syndromes observed with COVID-19.
PubDate: Thu, 29 Apr 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab010
Issue No: Vol. 62, No. 1-2 (2021)
- Animal Models of COVID-19. I. Comparative Virology and Disease
Pathogenesis-
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Authors: Zeiss C; Compton S, Veenhuis R.
Pages: 35 - 47
Abstract: The Coronavirus Disease 2019 (COVID-19) pandemic has fueled unprecedented development of animal models to understand disease pathogenesis, test therapeutics, and support vaccine development. Models previously developed to study severe acute respiratory syndrome coronavirus (SARS-CoV) have been rapidly deployed to study SARS-CoV-2. However, it has become clear that despite the common use of ACE2 as a receptor for both viruses, the host range of the 2 viruses does not entirely overlap. Distinct ACE2-interacting residues within the receptor binding domain of SARS-CoV and SARS-CoV-2, as well as species differences in additional proteases needed for activation and internalization of the virus, are likely sources of host differences between the 2 viruses. Spontaneous models include rhesus and cynomolgus macaques, African Green monkeys, hamsters, and ferrets. Viral shedding and transmission studies are more frequently reported in spontaneous models. Mice can be infected with SARS-CoV; however, mouse and rat ACE2 does not support SARS-CoV-2 infection. Murine models for COVID-19 are induced through genetic adaptation of SARS-CoV-2, creation of chimeric SARS-CoV and SARS-CoV-2 viruses, use of human ACE2 knock-in and transgenic mice, and viral transfection of wild-type mice with human ACE2. Core aspects of COVID-19 are faithfully reproduced across species and model. These include the acute nature and predominantly respiratory source of viral shedding, acute transient and nonfatal disease with a largely pulmonary phenotype, similar short-term immune responses, and age-enhanced disease. Severity of disease and tissue involvement (particularly brain) in transgenic mice varies by promoter. To date, these models have provided a remarkably consistent template on which to test therapeutics, understand immune responses, and test vaccine approaches. The role of comorbidity in disease severity and the range of severe organ-specific pathology in humans remains to be accurately modeled.
PubDate: Fri, 09 Apr 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab007
Issue No: Vol. 62, No. 1-2 (2021)
- Bioethical, Reproducibility, and Translational Challenges of Animal Models
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Authors: Landi M; Everitt J, Berridge B.
Pages: 60 - 65
Abstract: There is no prescribed stage or standardized point at which an animal model protocol is reviewed for reproducibility and translatability. The method of review for a reproducible and translatable study is not consistently documented in peer literature, and this is a major challenge for those working with animal models of human diseases. If the study is ill designed, it is impossible to perform an accurate harm/benefit analysis. In addition, there may be an ethical challenge if the work is not reproducible and translatable. Animal welfare regulations and other documents of control clearly state the role of the Institutional Animal Care and Use Committees are to look at science justification within the context of animal welfare. This article, concentrating on models not governed by regulations, outlines issues and offers recommendations for refining animal model review with a goal to improve study reproducibility and translatability.
PubDate: Mon, 08 Mar 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilaa027
Issue No: Vol. 62, No. 1-2 (2021)
- Research Relevant Background Lesions and Conditions: Ferrets, Dogs, Swine,
Sheep, and Goats-
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Authors: Helke K; Meyerholz D, Beck A, et al.
Pages: 133 - 168
Abstract: Animal models provide a valuable tool and resource for biomedical researchers as they investigate biological processes, disease pathogenesis, novel therapies, and toxicologic studies. Interpretation of animal model data requires knowledge not only of the processes/diseases being studied but also awareness of spontaneous conditions and background lesions in the model that can influence or even confound the study results. Species, breed/stock, sex, age, anatomy, physiology, diseases (noninfectious and infectious), and neoplastic processes are model features that can impact the results as well as study interpretation. Here, we review these features in several common laboratory animal species, including ferret, dog (beagle), pig, sheep, and goats.
PubDate: Sat, 13 Mar 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab005
Issue No: Vol. 62, No. 1-2 (2021)
- Research-Relevant Background Lesions and Conditions in Common Avian and
Aquatic Species-
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Authors: Mangus L; França M, Shivaprasad H, et al.
Pages: 169 - 202
Abstract: Non-mammalian vertebrates including birds, fish, and amphibians have a long history of contributing to ground-breaking scientific discoveries. Because these species offer several experimental advantages over higher vertebrates and share extensive anatomic and genetic homology with their mammalian counterparts, they remain popular animal models in a variety of fields such as developmental biology, physiology, toxicology, drug discovery, immunology, toxicology, and infectious disease. As with all animal models, familiarity with the anatomy, physiology, and spontaneous diseases of these species is necessary for ensuring animal welfare, as well as accurate interpretation and reporting of study findings. Working with avian and aquatic species can be especially challenging in this respect due to their rich diversity and array of unique adaptations. Here, we provide an overview of the research-relevant anatomic features, non-infectious conditions, and infectious diseases that impact research colonies of birds and aquatic animals, including fish and Xenopus species.
PubDate: Tue, 30 Mar 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab008
Issue No: Vol. 62, No. 1-2 (2021)
- Research-Relevant Clinical Pathology Resources: Emphasis on Mice, Rats,
Rabbits, Dogs, Minipigs, and Non-Human Primates-
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Authors: Bau-Gaudreault L; Arndt T, Provencher A, et al.
Pages: 203 - 222
Abstract: Clinical pathology testing for investigative or biomedical research and for preclinical toxicity and safety assessment in laboratory animals is a distinct specialty requiring an understanding of species specific and other influential variables on results and interpretation. This review of clinical pathology principles and testing recommendations in laboratory animal species aims to provide a useful resource for researchers, veterinary specialists, toxicologists, and clinical or anatomic pathologists.
PubDate: Mon, 06 Dec 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab028
Issue No: Vol. 62, No. 1-2 (2021)
- Biomonitoring and Digital Data Technology as an Opportunity for Enhancing
Animal Study Translation-
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Authors: Defensor E; Lim M, Schaevitz L.
Pages: 223 - 231
Abstract: The failure of animal studies to translate to effective clinical therapeutics has driven efforts to identify underlying cause and develop solutions that improve the reproducibility and translatability of preclinical research. Common issues revolve around study design, analysis, and reporting as well as standardization between preclinical and clinical endpoints. To address these needs, recent advancements in digital technology, including biomonitoring of digital biomarkers, development of software systems and database technologies, as well as application of artificial intelligence to preclinical datasets can be used to increase the translational relevance of preclinical animal research. In this review, we will describe how a number of innovative digital technologies are being applied to overcome recurring challenges in study design, execution, and data sharing as well as improving scientific outcome measures. Examples of how these technologies are applied to specific therapeutic areas are provided. Digital technologies can enhance the quality of preclinical research and encourage scientific collaboration, thus accelerating the development of novel therapeutics.
PubDate: Mon, 07 Jun 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab018
Issue No: Vol. 62, No. 1-2 (2021)
- Type I Hypersensitivity in Ferrets Following Exposure to SARS-CoV-2
Inoculum: Lessons Learned-
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Authors: Layton D; Burkett K, Marsh G, et al.
Pages: 232 - 237
Abstract: 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.
PubDate: Wed, 23 Jun 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab019
Issue No: Vol. 62, No. 1-2 (2021)
- Mouse Anesthesia: The Art and Science
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Authors: Navarro K; Huss M, Smith J, et al.
Pages: 238 - 273
Abstract: There is an art and science to performing mouse anesthesia, which is a significant component to animal research. Frequently, anesthesia is one vital step of many over the course of a research project spanning weeks, months, or beyond. It is critical to perform anesthesia according to the approved research protocol using appropriately handled and administered pharmaceutical-grade compounds whenever possible. Sufficient documentation of the anesthetic event and procedure should also be performed to meet the legal, ethical, and research reproducibility obligations. However, this regulatory and documentation process may lead to the use of a few possibly oversimplified anesthetic protocols used for mouse procedures and anesthesia. Although a frequently used anesthetic protocol may work perfectly for each mouse anesthetized, sometimes unexpected complications will arise, and quick adjustments to the anesthetic depth and support provided will be required. As an old saying goes, anesthesia is 99% boredom and 1% sheer terror. The purpose of this review article is to discuss the science of mouse anesthesia together with the art of applying these anesthetic techniques to provide readers with the knowledge needed for successful anesthetic procedures. The authors include experiences in mouse inhalant and injectable anesthesia, peri-anesthetic monitoring, specific procedures, and treating common complications. This article utilizes key points for easy access of important messages and authors’ recommendation based on the authors’ clinical experiences.
PubDate: Mon, 28 Jun 2021 00:00:00 GMT
DOI: 10.1093/ilar/ilab016
Issue No: Vol. 62, No. 1-2 (2021)
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