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The Journal of Allergy and Clinical... Feb 2021Research into the pathophysiology of psoriasis remains challenging, because this disease does not occur naturally in laboratory animals. However, specific aspects of its... (Review)
Review
Research into the pathophysiology of psoriasis remains challenging, because this disease does not occur naturally in laboratory animals. However, specific aspects of its complex immune-pathology can be illuminated through transgenic, knockout, xenotransplantation, immunological reconstitution, drug-induced, or spontaneous mutation models in rodents. Although some of these approaches have already been pursued for more than 5 decades and even more models have been described in recent times, they have surprisingly not yet been systematically validated. As a consequence, researchers regularly examine specific aspects that only partially reflect the complex overall picture of the human disease. Nonetheless, animal models are of great utility to investigate inflammatory mediators, the communication between cells of the innate and the adaptive immune systems, the role of resident cells as well as new therapies. Of note, various manipulations in experimental animals resulted in rather similar phenotypes. These were called "psoriasiform", "psoriasis-like" or even "psoriasis" usually on the basis of some similarities with the human disorder. Xenotransplantation of human skin onto immunocompromised animals can overcome this limitation only in part. In this review, we elucidate approaches for the generation of animal models of psoriasis and assess their strengths and limitations with a certain focus on more recently developed models.
Topics: Animals; Disease Models, Animal; Humans; Psoriasis
PubMed: 32560971
DOI: 10.1016/j.jaci.2020.04.034 -
Medicina (Kaunas, Lithuania) Feb 2022Recently, increased interest and efforts were observed in describing the possible interaction between sleep and emotions. Human and animal model studies addressed the... (Review)
Review
Recently, increased interest and efforts were observed in describing the possible interaction between sleep and emotions. Human and animal model studies addressed the implication of both sleep patterns and emotional processing in neurophysiology and neuropathology in suggesting a bidirectional interaction intimately modulated by complex mechanisms and factors. In this context, we aimed to discuss recent evidence and possible mechanisms implicated in this interaction, as provided by both human and animal models in studies. In addition, considering the affective component of brain physiological patterns, we aimed to find reasonable evidence in describing the two-way association between comorbid sleep impairments and psychiatric disorders. The main scientific literature databases (PubMed/Medline, Web of Science) were screened with keyword combinations for relevant content taking into consideration only English written papers and the inclusion and exclusion criteria, according to PRISMA guidelines. We found that a strong modulatory interaction between sleep processes and emotional states resides on the activity of several key brain structures, such as the amygdala, prefrontal cortex, hippocampus, and brainstem nuclei. In addition, evidence suggested that physiologically and behaviorally related mechanisms of sleep are intimately interacting with emotional perception and processing which could advise the key role of sleep in the unconscious character of emotional processes. However, further studies are needed to explain and correlate the functional analysis with causative and protective factors of sleep impairments and negative emotional modulation on neurophysiologic processing, mental health, and clinical contexts.
Topics: Amygdala; Animals; Brain; Emotions; Humans; Magnetic Resonance Imaging; Models, Animal; Sleep
PubMed: 35208598
DOI: 10.3390/medicina58020274 -
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 -
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 -
International Journal of Molecular... Feb 2023Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly... (Review)
Review
Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has strong genetic determinants, and genetic variants in more than 25 genes have been identified to be associated with ACM, accounting for approximately 60% of ACM cases. Genetic studies of ACM in vertebrate animal models such as zebrafish (), which are highly amenable to large-scale genetic and drug screenings, offer unique opportunities to identify and functionally assess new genetic variants associated with ACM and to dissect the underlying molecular and cellular mechanisms at the whole-organism level. Here, we summarize key genes implicated in ACM. We discuss the use of zebrafish models, categorized according to gene manipulation approaches, such as gene knockdown, gene knock-out, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, to study the genetic underpinning and mechanism of ACM. Information gained from genetic and pharmacogenomic studies in such animal models can not only increase our understanding of the pathophysiology of disease progression, but also guide disease diagnosis, prognosis, and the development of innovative therapeutic strategies.
Topics: Animals; Zebrafish; Arrhythmogenic Right Ventricular Dysplasia; Models, Animal; Arrhythmias, Cardiac; Death, Sudden, Cardiac
PubMed: 36835518
DOI: 10.3390/ijms24044106 -
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 -
Arthritis Research & Therapy 2013Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of... (Review)
Review
Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles.
Topics: Animals; Disease Models, Animal; Fibromyalgia
PubMed: 24314231
DOI: 10.1186/ar4402