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Advances in Experimental Medicine and... 2020Genetic model systems allow researchers to probe and decipher aspects of human disease, and animal models of disease are frequently specifically engineered and have been... (Review)
Review
Genetic model systems allow researchers to probe and decipher aspects of human disease, and animal models of disease are frequently specifically engineered and have been identified serendipitously as well. Animal models are useful for probing the etiology and pathophysiology of disease and are critical for effective discovery and development of novel therapeutics for rare diseases. Here we review the impact of animal model organism research in three examples of congenital metabolic disorders to highlight distinct advantages of model system research. First, we discuss phenylketonuria research where a wide variety of research fields and models came together to make impressive progress and where a nearly ideal mouse model has been central to therapeutic advancements. Second, we review advancements in Lesch-Nyhan syndrome research to illustrate the role of models that do not perfectly recapitulate human disease as well as the need for multiple models of the same disease to fully investigate human disease aspects. Finally, we highlight research on the GM2 gangliosidoses Tay-Sachs and Sandhoff disease to illustrate the important role of both engineered traditional laboratory animal models and serendipitously identified atypical models in congenital metabolic disorder research. We close with perspectives for the future for animal model research in congenital metabolic disorders.
Topics: Animals; Disease Models, Animal; Gangliosidoses, GM2; Humans; Metabolism, Inborn Errors; Rare Diseases; Sandhoff Disease; Tay-Sachs Disease
PubMed: 32304075
DOI: 10.1007/978-981-15-2389-2_9 -
Experimental Neurology Jun 2020This report was produced by an Expert Working Group (EWG) consisting of UK-based researchers, veterinarians and regulators of animal experiments with specialist... (Review)
Review
This report was produced by an Expert Working Group (EWG) consisting of UK-based researchers, veterinarians and regulators of animal experiments with specialist knowledge of the use of animal models of spinal cord injury (SCI). It aims to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Specific animal welfare issues were identified and discussed, and practical measures proposed, with the aim of reducing animal use and suffering, reducing experimental variability, and increasing translatability within this critically important research field.
Topics: Animal Welfare; Animals; Disease Models, Animal; Rodentia; Spinal Cord Injuries
PubMed: 32142803
DOI: 10.1016/j.expneurol.2020.113273 -
Frontiers in Cellular and Infection... 2024Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where... (Review)
Review
Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population. The common marmoset (), a Neotropical new-world (platyrrhines) non-human primate, has gained increasing attention as an animal model for a number of diseases given its small size, availability and evolutionary proximity to humans. This review aims to (i) discuss the pros and cons of the common marmoset as an animal model by providing a brief snapshot of how marmosets are currently utilized in biomedical research, (ii) summarize and evaluate relevant aspects of the marmoset immune system to the study of infectious diseases, (iii) provide a historical backdrop, outlining the significance of infectious diseases and the importance of developing reliable animal models to test novel therapeutics, and (iv) provide a summary of infectious diseases for which a marmoset model exists, followed by an in-depth discussion of the marmoset models of two studied bacterial infectious diseases (tularemia and melioidosis) and one viral infectious disease (viral hepatitis C).
Topics: Animals; Humans; Callithrix; Disease Models, Animal; Communicable Diseases; Tularemia; Bacterial Infections
PubMed: 38465237
DOI: 10.3389/fcimb.2024.1340017 -
Behavioral and Brain Functions : BBF Feb 2017Animal models of human behavioural deficits involve conducting experiments on animals with the hope of gaining new knowledge that can be applied to humans. This paper... (Review)
Review
BACKGROUND
Animal models of human behavioural deficits involve conducting experiments on animals with the hope of gaining new knowledge that can be applied to humans. This paper aims to address risks, biases, and fallacies associated with drawing conclusions when conducting experiments on animals, with focus on animal models of mental illness.
CONCLUSIONS
Researchers using animal models are susceptible to a fallacy known as false analogy, where inferences based on assumptions of similarities between animals and humans can potentially lead to an incorrect conclusion. There is also a risk of false positive results when evaluating the validity of a putative animal model, particularly if the experiment is not conducted double-blind. It is further argued that animal model experiments are reconstructions of human experiments, and not replications per se, because the animals cannot follow instructions. This leads to an experimental setup that is altered to accommodate the animals, and typically involves a smaller sample size than a human experiment. Researchers on animal models of human behaviour should increase focus on mechanistic validity in order to ensure that the underlying causal mechanisms driving the behaviour are the same, as relying on face validity makes the model susceptible to logical fallacies and a higher risk of Type 1 errors. We discuss measures to reduce bias and risk of making logical fallacies in animal research, and provide a guideline that researchers can follow to increase the rigour of their experiments.
Topics: Animals; Biomedical Research; Disease Models, Animal; Humans; Logic; Mental Disorders
PubMed: 28202023
DOI: 10.1186/s12993-017-0121-8 -
Microbes and Environments Dec 2017The ecosystem of the human gastrointestinal (GI) tract traverses a number of environmental, chemical, and physical conditions because it runs from the oral cavity to the... (Review)
Review
The ecosystem of the human gastrointestinal (GI) tract traverses a number of environmental, chemical, and physical conditions because it runs from the oral cavity to the anus. These differences in conditions along with food or other ingested substrates affect the composition and density of the microbiota as well as their functional roles by selecting those that are the most suitable for that environment. Previous studies have mostly focused on Bacteria, with the number of studies conducted on Archaea, Eukarya, and Viruses being limited despite their important roles in this ecosystem. Furthermore, due to the challenges associated with collecting samples directly from the inside of humans, many studies are still exploratory, with a primary focus on the composition of microbiomes. Thus, mechanistic studies to investigate functions are conducted using animal models. However, differences in physiology and microbiomes need to be clarified in order to aid in the translation of animal model findings into the context of humans. This review will highlight Bacteria, Archaea, Fungi, and Viruses, discuss differences along the GI tract of healthy humans, and perform comparisons with three common animal models: rats, mice, and pigs.
Topics: Animals; Archaea; Bacteria; Biodiversity; Diet; Food; Fungi; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Mice; Models, Animal; Rats; Swine; Viruses
PubMed: 29129876
DOI: 10.1264/jsme2.ME17017 -
Current Opinion in Virology Oct 2015Any one model system, be it culture or animal, only recapitulates one aspect of the viral life cycle in the human host. By providing recent examples of animal models for... (Review)
Review
Any one model system, be it culture or animal, only recapitulates one aspect of the viral life cycle in the human host. By providing recent examples of animal models for Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus, we would argue that multiple animal models are needed to gain a comprehensive understanding of the pathogenesis associated with human oncogenic herpesviruses. Transgenic mice, homologous animal herpesviruses, and tumorgraft and humanized mouse models all complement each other in the study of viral pathogenesis. The use of animal model systems facilitates the exploration of novel anti-viral and anti-cancer treatment modalities for diseases associated with oncogenic herpesviruses.
Topics: Animals; Carcinogenesis; Disease Models, Animal; Herpesviridae; Herpesviridae Infections; Host-Pathogen Interactions; Humans; Mice; Oncogenic Viruses
PubMed: 26476352
DOI: 10.1016/j.coviro.2015.09.006 -
Handbook of Experimental Pharmacology 2019With the approval of calcitonin gene-related peptide (CGRP) and CGRP receptor monoclonal antibodies by the Federal Drug Administration, a new era in the treatment of... (Review)
Review
With the approval of calcitonin gene-related peptide (CGRP) and CGRP receptor monoclonal antibodies by the Federal Drug Administration, a new era in the treatment of migraine patients is beginning. However, there are still many unknowns in terms of CGRP mechanisms of action that need to be elucidated to allow new advances in migraine therapies. CGRP has been studied both clinically and preclinically since its discovery. Here we review some of the preclinical data regarding CGRP in animal models of migraine.
Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Models, Animal; Receptors, Calcitonin Gene-Related Peptide
PubMed: 30689086
DOI: 10.1007/164_2018_187 -
Osteoarthritis and Cartilage Feb 2019Osteoarthritis (OA) is a chronic degenerative disease of diarthrodial joints most commonly affecting people over the age of forty. The causes of OA are still unknown and... (Review)
Review
Osteoarthritis (OA) is a chronic degenerative disease of diarthrodial joints most commonly affecting people over the age of forty. The causes of OA are still unknown and there is much debate in the literature as to the exact sequence of events that trigger the onset of the heterogeneous disease we recognise as OA. There is currently no consensus model for OA that naturally reflects human disease. Existing ex-vivo models do not incorporate the important inter-tissue communication between joint components required for disease progression and differences in size, anatomy, histology and biomechanics between different animal models makes translation to the human model very difficult. This narrative review highlights the advantages and disadvantages of the current models used to study OA. It discusses the challenges of producing a more reliable OA-model and proposes a direction for the development of a consensus model that reflects the natural environment of human OA. We suggest that a human osteochondral plug-based model may overcome many of the fundamental limitations associated with animal and in-vitro models based on isolated cells. Such a model will also provide a platform for the development and testing of targeted treatment and validation of novel OA markers directly on human tissues.
Topics: Animals; Arthritis, Experimental; Biomedical Research; Bone Transplantation; Cell Culture Techniques; Humans; Osteoarthritis; Species Specificity
PubMed: 30391394
DOI: 10.1016/j.joca.2018.09.016 -
International Journal of Medical... 2023Numerous preclinical models have been developed to advance biomedical research in type 1 diabetes mellitus (T1DM). They are essential for improving our knowledge of T1DM... (Review)
Review
Numerous preclinical models have been developed to advance biomedical research in type 1 diabetes mellitus (T1DM). They are essential for improving our knowledge of T1DM development and progression, allowing researchers to identify potential therapeutic targets and evaluate the effectiveness of new medications. A deeper comprehension of these models themselves is critical not only to determine the optimal strategies for their utilization but also to fully unlock their potential applications in both basic and translational research. Here, we will comprehensively summarize and discuss the applications, advantages, and limitations of the commonly used animal models for human T1DM and also overview the up-to-date human tissue bioengineering models for the investigation of T1DM. By combining these models with a better understanding of the pathophysiology of T1DM, we can enhance our insights into disease initiation and development, ultimately leading to improved therapeutic responses and outcomes.
Topics: Animals; Humans; Diabetes Mellitus, Type 1; Models, Animal; Biomedical Research
PubMed: 37859703
DOI: 10.7150/ijms.86566 -
FEMS Microbiology Reviews May 2023Periodontitis and caries are driven by complex interactions between the oral microbiome and host factors, i.e. inflammation and dietary sugars, respectively. Animal... (Review)
Review
Periodontitis and caries are driven by complex interactions between the oral microbiome and host factors, i.e. inflammation and dietary sugars, respectively. Animal models have been instrumental in our mechanistic understanding of these oral diseases, although no single model can faithfully reproduce all aspects of a given human disease. This review discusses evidence that the utility of an animal model lies in its capacity to address a specific hypothesis and, therefore, different aspects of a disease can be investigated using distinct and complementary models. As in vitro systems cannot replicate the complexity of in vivo host-microbe interactions and human research is typically correlative, model organisms-their limitations notwithstanding-remain essential in proving causality, identifying therapeutic targets, and evaluating the safety and efficacy of novel treatments. To achieve broader and deeper insights into oral disease pathogenesis, animal model-derived findings can be synthesized with data from in vitro and clinical research. In the absence of better mechanistic alternatives, dismissal of animal models on fidelity issues would impede further progress to understand and treat oral disease.
Topics: Animals; Humans; Periodontitis; Microbiota; Host Microbial Interactions; Models, Animal; Dysbiosis
PubMed: 37113021
DOI: 10.1093/femsre/fuad018