Difficulties with Animal Models: Chimpanzee Research

1995 ◽  
Vol 23 (5) ◽  
pp. 592-597
Author(s):  
Stephen Kaufman
Keyword(s):  
Animal Model ◽  
Human Physiology ◽  
Animal Models ◽  
Natural History ◽  
Biomedical Research ◽  
Human Condition ◽  
Interspecies Differences ◽  
Anatomy And Physiology ◽  
Model Condition

Animal models are generally used to elucidate human physiology or pathology. However, attempts to extrapolate animal model findings to humans are undermined by differences in the aetiology and natural history between any animal model condition and the analogous human condition, and by unavoidable interspecies differences in anatomy and physiology. Even when working with species “closely related” to humans, such as chimpanzees, the animal model paradigm is fundamentally unsound. Unfortunately, few animal researchers seriously question the utility of animal models, and consequently they rarely consider other, perhaps more efficient and more reliable, means of conducting biomedical research.

Recent advances in animal model experimentation in autism research

2013 ◽  
Vol 26 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Mousumi Tania ◽  
Md. Asaduzzaman Khan ◽  
Kun Xia
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Human Condition ◽  
Behavioral Alterations ◽  
Important Place ◽  
Adult Mice ◽  
Recent Advances ◽  
Model Study ◽  
Disease Biology ◽  
Animal Model Study

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

scholarly journals Embryo-Based Large Fragment Knock-in in Mammals: Why, How and What’s Next

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 140 ◽  
Author(s):  
Steven Erwood ◽  
Bin Gu
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Genome Editing ◽  
Biomedical Research ◽  
Future Development ◽  
Genetic Modification ◽  
Technological Innovations ◽  
Model Generation ◽  
Large Fragment ◽  
Diverse Range

Endonuclease-mediated genome editing technologies, most notably CRISPR/Cas9, have revolutionized animal genetics by allowing for precise genome editing directly through embryo manipulations. As endonuclease-mediated model generation became commonplace, large fragment knock-in remained one of the most challenging types of genetic modification. Due to their unique value in biological and biomedical research, however, a diverse range of technological innovations have been developed to achieve efficient large fragment knock-in in mammalian animal model generation, with a particular focus on mice. Here, we first discuss some examples that illustrate the importance of large fragment knock-in animal models and then detail a subset of the recent technological advancements that have allowed for efficient large fragment knock-in. Finally, we envision the future development of even larger fragment knock-ins performed in even larger animal models, the next step in expanding the potential of large fragment knock-in in animal models.

Animal models of psychosis

2020 ◽  
pp. 496-506
Author(s):  
Daniel Scott
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Psychiatric Illness ◽  
Behavioral Assessment ◽  
Underlying Disease ◽  
Human Condition ◽  
Model Systems ◽  
Behavioral Assessments ◽  
Validity Measures ◽  
Valid Animal Model

The creation of a valid animal model is of crucial importance to the study of the biological mechanisms underlying disease pathophysiology. This becomes difficult when studying psychiatric illness, most especially psychosis, as humans’ mental state is a strictly internally experienced phenomenon, and thus the biological readout of these conditions is often a behavioral assessment. Therefore, when designing appropriate animal model systems and behavioral assessments for the study of psychiatric illness, it is necessary that appropriate measures be taken to ensure the systems and tasks used fulfill rigorous demands of validity. This chapter discusses different forms of validity, expanding on the classical validity measures of face, predictive, and construct validity. Specific examples of behavioral assessments and animal preparations that adhere to these specific definitions of validity are presented. These include specific experimental paradigms that can be similarly assessed in humans with psychosis and animal models, methods to create an animal preparation based on known psychosis triggers and risk factors, and pharmacological means to demonstrate relevance to the human condition. The chapter argues for a systematic approach to design, verify, and validate an animal model system for research into psychosis specifically, and other psychiatric disorders more generally, based on these different classes of validity.

THE USE OF RUMINANTS FOR BIOMEDICAL RESEARCH IN PERINATALOGY

2012 ◽  
Vol 24 (1) ◽  
pp. 286
Author(s):  
Pascale Chavatte-Palmer ◽  
Anne Tarrade ◽  
Vassilis Tsatsaris ◽  
Olivier Morel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Biomedical Research ◽  
Low Cost ◽  
Genetic Research ◽  
Surgical Approaches ◽  
Gestation Length ◽  
Large Animal ◽  
Pubmed Database ◽  
Wide Range

As a consequence of obvious ethical considerations concerning what is feasible or not in the field of human biomedical research, animal models are of critical importance both for human and veterinary medicine and cognitive scientists. Many species have been and are currently used as animal models. Rodents and lagomorphs are the most popular, essentially because of their low cost, handling and rearing facilities, limited ethical impact, and the availability of a wide range of genetic research tools in these species. Nevertheless, these models present some limitations. The physiological mechanisms observed in these species might be far from those of humans. For example, due to the large number of embryos and short gestation length, rodents and lagomorphs are not very suitable in several fields of perinatal research. Large animal species are required when surgical approaches or new medical devices have to be evaluated. The pig is widely used in these situations, as well as ruminants such as the sheep and the goat. Concerning physiological, anatomical and genetic considerations, large primates could be considered as the “gold standard” animal model because of their important similarities with humans. However, their use for biomedical research is greatly limited by their behavioral and social organization, raising important ethical questions, and their elevated cost. A very large number of experiments using ruminants as animal models have been published. A rapid bibliometric analysis performed using the Pubmed database from 1969 to 2010 retrieved 1108 literature reviews using the Mesh keywords “ruminant & animal model”. Six hundred and twelve references were available only for the year 2009 using the same Mesh research and covering all types of publications. The sheep is the most widely used ruminant model, and no less than 5393 publications can be found using the Mesh keywords “sheep & animal model”. The current presentation will focus on the most outstanding examples of great biomedical advances carried out with ruminant as models in the field of perinatal research. In this paper, the pivotal role of ruminants in the evaluation and development of new pharmacological treatments, new invasive procedures in fetuses, gestational imaging and genetic approaches will be developed, with their clinical context, including our own work on feto-placental imaging and the assessment of placental blood flow using quantitative 3D Doppler.

scholarly journals The influence of host genetics, virome, and gut microbiota transfer methods in mouse model reproducibility

2021 ◽  
Author(s):  
◽  
Chunye Zhang
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Mouse Model ◽  
Biomedical Research ◽  
Gold Standard ◽  
Genetic Background ◽  
Transfer Efficiency ◽  
Animal Disease ◽  
Disease Phenotype ◽  
Transfer Method

Gut microbiome (GM), the complex community that combines all bacteria, viruses, protozoa, and fungi located in the gut of human or animal, plays a significant role in host health and disease. Animal model are widely used to investigate human disease in biomedical research. The GM differs in animal models results from many factors such as vendors, facilitates, husbandry, environment, etc. The variation of GM can contribute to the difference of the disease phenotype in animal models which results in poor reproducibility and repeatability in biomedical research. The differences in the gut virome can also impact the repeatability between animal models and contribute to the poor translatability of animal disease models to human disease due to less pathogen exposure in lab animals. The different methods of GM modulation also can lead to differences between animal models of disease. In this project, first, we investigated the potential contributors to research repeatability and translatability of animal models by characterizing the gut virome differences between mice from different sources including pet stores and different laboratories. Second, we assessed the role of differing GM transfer methods of efficiency and completeness of transfer of GM and impact of transfer on the DSS model of colitis. Ultimately to explore and provide a better way for the biomedical research community to do the GM transfer with higher transfer efficiency and more practical in any genetically modified animal disease model with desired GM. We applied the gold standard GM transfer method, embryo transfer (ET), to assess the genetic background and GM contributing to the GM transfer efficiency and subsequent disease phenotype in animal model. We transferred well-established richness GM4 and low richness GM1 to two different substrain B6J and B6N mice to assess the GM and genetic influence on the recipient mice and the subsequent influence on disease phenotype in DSS-induced chronic colitis mouse model. We found that both GM and substrain genetic background contributing to the GM transfer efficiency and have an influence on the disease phenotype in mouse models. We then designed experiments using the same GM transfer to the same genetic background recipient mice to compare and investigated the different transfer methods (standard ET, commonly used co-house, and newly explored cross-foster) influence on GM transfer efficiency in animal models and subsequent influence on disease phenotype. In conclusion, by comparing the gut virome of standard lab mice and presumably more antigen-experienced wild and pet store mice we explored how informative and translational standard lab mice are in contemporary biomedical research and by comparing the gut virome of mice from different vendors the project addressed one of the possible causes of poor reproducibility in biomedical research that uses mice. We investigated and determined whether differing GM transfer methods and the associated differences in GM transfer efficiency result in differences in animal model phenotypes using the DSS model of colitis. We also established efficient and economically feasible methods of GM transfer that can be applied to any genetically engineered mouse model of disease. Cross-foster could be used as an alternate GM transfer method to transfer the same desired GM to an animal model if the gold standard ET is not available in the lab. The result generated using co-house method as a GM-associated modulation manner should be interpreted with caution.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

scholarly journals Consideration of Gut Microbiome in Murine Models of Diseases

2021 ◽  
Vol 9 (5) ◽  
pp. 1062
Author(s):  
Chunye Zhang ◽  
Craig L. Franklin ◽  
Aaron C. Ericsson
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Biomedical Research ◽  
Gut Microbiome ◽  
Close Association ◽  
Disease Model ◽  
Potential Contributor ◽  
Potential Factors ◽  
Models Of Disease ◽  
The Impact

The gut microbiome (GM), a complex community of bacteria, viruses, protozoa, and fungi located in the gut of humans and animals, plays significant roles in host health and disease. Animal models are widely used to investigate human diseases in biomedical research and the GM within animal models can change due to the impact of many factors, such as the vendor, husbandry, and environment. Notably, variations in GM can contribute to differences in disease model phenotypes, which can result in poor reproducibility in biomedical research. Variation in the gut microbiome can also impact the translatability of animal models. For example, standard lab mice have different pathogen exposure experiences when compared to wild or pet store mice. As humans have antigen experiences that are more similar to the latter, the use of lab mice with more simplified microbiomes may not yield optimally translatable data. Additionally, the literature describes many methods to manipulate the GM and differences between these methods can also result in differing interpretations of outcomes measures. In this review, we focus on the GM as a potential contributor to the poor reproducibility and translatability of mouse models of disease. First, we summarize the important role of GM in host disease and health through different gut–organ axes and the close association between GM and disease susceptibility through colonization resistance, immune response, and metabolic pathways. Then, we focus on the variation in the microbiome in mouse models of disease and address how this variation can potentially impact disease phenotypes and subsequently influence research reproducibility and translatability. We also discuss the variations between genetic substrains as potential factors that cause poor reproducibility via their effects on the microbiome. In addition, we discuss the utility of complex microbiomes in prospective studies and how manipulation of the GM through differing transfer methods can impact model phenotypes. Lastly, we emphasize the need to explore appropriate methods of GM characterization and manipulation.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals Methods Used and Application of the Mouse Grimace Scale in Biomedical Research 10 Years On: A Scoping Review

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Biomedical Research ◽  
Scoping Review ◽  
Facial Features ◽  
Inclusion Criteria ◽  
Academic Literature ◽  
Research Fields ◽  
Neuroscience Research ◽  
Wide Range

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.

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