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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 -
Viruses Jan 2023The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to... (Review)
Review
The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to study virus pathogenicity and to develop medical countermeasures. As these have inherent shortcomings, the rise of microphysiological systems and organoids able to recapitulate hallmarks of the diseases caused by these viruses may have enormous potential to add to or partially replace animal modeling in the future. Indeed, microphysiological systems and organoids are already used in the pharmaceutical R&D pipeline because they are prefigured to overcome the translational gap between model systems and clinical studies. Moreover, they may serve to alleviate ethical concerns related to animal research. In this review, we discuss the value of animal model alternatives in human pathogenic filovirus and bornavirus research. The current animal models and their limitations are presented followed by an overview of existing alternatives, such as organoids and microphysiological systems, which might help answering open research questions.
Topics: Animals; Humans; Filoviridae; Bornaviridae; Models, Animal
PubMed: 36680198
DOI: 10.3390/v15010158 -
ACS Chemical Neuroscience Aug 2018
Topics: Animals; Models, Animal; Nervous System Physiological Phenomena; Neurosciences
PubMed: 30107742
DOI: 10.1021/acschemneuro.8b00380 -
International Journal of Surgery... Dec 2019Animal models have provided invaluable information in the pursuit of medical knowledge and alleviation of human suffering. The foundations of our basic understanding of... (Review)
Review
Animal models have provided invaluable information in the pursuit of medical knowledge and alleviation of human suffering. The foundations of our basic understanding of disease pathophysiology and human anatomy can largely be attributed to preclinical investigations using various animal models. Recently, however, the scientific community, citing concerns about animal welfare as well as the validity and applicability of outcomes, has called the use of animals in research into question. In this review, we seek to summarize the current state of the use of animal models in research.
Topics: Animal Experimentation; Animal Testing Alternatives; Animal Welfare; Animals; Data Interpretation, Statistical; Disease Models, Animal; Humans; Models, Animal; Research Design; Species Specificity; Translational Research, Biomedical
PubMed: 31627013
DOI: 10.1016/j.ijsu.2019.10.015 -
CNS Neuroscience & Therapeutics Jun 2021Depressive disorder is one of the most widespread forms of psychiatric pathology, worldwide. According to a report by the World Health Organization, the number of people... (Review)
Review
Depressive disorder is one of the most widespread forms of psychiatric pathology, worldwide. According to a report by the World Health Organization, the number of people with depression, globally, is increasing dramatically with each year. Previous studies have demonstrated that various factors, including genetics and environmental stress, contribute to the risk of depression. As such, it is crucial to develop a detailed understanding of the pathogenesis of depressive disorder and animal studies are essential for identifying the mechanisms and genetic disorders underlying depression. Recently, many researchers have reported on the pathology of depression via various models of depressive disorder. Given that different animal models of depression show differences in terms of patterns of depressive behavior and pathology, the comparison between depressive animal models is necessary for progress in the field of the depression study. However, the various animal models of depression have not been fully compared or evaluated until now. In this paper, we reviewed the pathophysiology of the depressive disorder and its current animal models with the analysis of their transcriptomic profiles. We provide insights for selecting different animal models for the study of depression.
Topics: Animals; Depressive Disorder; Disease Models, Animal; Humans; Species Specificity
PubMed: 33650178
DOI: 10.1111/cns.13622 -
Stem Cell Research & Therapy May 2023Incidence of premature ovarian failure (POF) is higher with the increase of the pace of life. The etiology of POF is very complex, which is closely related to genes,... (Review)
Review
Incidence of premature ovarian failure (POF) is higher with the increase of the pace of life. The etiology of POF is very complex, which is closely related to genes, immune diseases, drugs, surgery, and psychological factors. Ideal animal models and evaluation indexes are essential for drug development and mechanism research. In our review, we firstly summarize the modeling methods of different POF animal models and compare their advantages and disadvantages. Recently, stem cells are widely studied for tumor treatment and tissue repair with low immunogenicity, high homing ability, high ability to divide and self-renew. Hence, we secondly reviewed recently published data on transplantation of stem cells in the POF animal model and analyzed the possible mechanism of their function. With the further insights of immunological and gene therapy, the combination of stem cells with other therapies should be actively explored to promote the treatment of POF in the future. Our article may provide guidance and insight for POF animal model selection and new drug development.
Topics: Female; Humans; Animals; Primary Ovarian Insufficiency; Disease Models, Animal; Mesenchymal Stem Cell Transplantation
PubMed: 37202808
DOI: 10.1186/s13287-023-03333-4 -
Journal of Biomedicine & Biotechnology 2012Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an... (Review)
Review
Dermatophytosis is superficial fungal infection caused by dermatophytes that invade the keratinized tissue of humans and animals. Lesions from dermatophytosis exhibit an inflammatory reaction induced to eliminate the invading fungi by using the host's normal immune function. Many scientists have attempted to establish an experimental animal model to elucidate the pathogenesis of human dermatophytosis and evaluate drug efficacy. However, current animal models have several issues. In the present paper, we surveyed reports about the methodology of the dermatophytosis animal model for tinea corporis, tinea pedis, and tinea unguium and discussed future prospects.
Topics: Animals; Disease Models, Animal; Humans; Tinea
PubMed: 22619489
DOI: 10.1155/2012/125384 -
The American Journal of Pathology Feb 2021Over the past 30 years, a range of cystic fibrosis (CF) animal models have been generated for research purposes. Different species, including mice, rats, ferrets,... (Review)
Review
Over the past 30 years, a range of cystic fibrosis (CF) animal models have been generated for research purposes. Different species, including mice, rats, ferrets, rabbits, pigs, sheep, zebrafish, and fruit flies, have all been used to model CF disease. While access to such a variety of animal models is a luxury for any research field, it also complicates the decision-making process when it comes to selecting the right model for an investigation. The purpose of this review is to provide a guide for selecting the most appropriate CF animal model for any given application. In this review, the characteristics and phenotypes of each animal model are described, along with a discussion of the key considerations that must be taken into account when choosing a suitable animal model. Available in vitro systems of CF are also described and can offer a useful alternative to using animal models. Finally, the future of CF animal model generation and its use in research are speculated upon.
Topics: Animals; Cell Culture Techniques; Cystic Fibrosis; Disease Models, Animal
PubMed: 33232694
DOI: 10.1016/j.ajpath.2020.10.017 -
Pediatrics International : Official... May 2021Bronchopulmonary dysplasia (BPD) is a serious complication of preterm delivery and low birthweight infants. The incidence of BPD has not decreased, and there is no... (Review)
Review
Bronchopulmonary dysplasia (BPD) is a serious complication of preterm delivery and low birthweight infants. The incidence of BPD has not decreased, and there is no effective treatment for the disease. Since the survival rate of premature infants has increased, it has become difficult to obtain pathological tissue samples from BPD death cases. There is also no in vitro experimental system for complex three-dimensional structures, such as alveolarization and pulmonary angiogenesis; thus, the use of animal models is necessary to elucidate the pathology of BPD and develop new treatments. To date, BPD animal models were being developed by exposing immature animal lungs to various stimuli. In the present review, I summarize BPD animal models that use (i) highly concentrated oxygen, (ii) mechanical ventilation, and (iii) infection/inflammation. In addition, with mesenchymal stromal cell (MSC) therapy for BPD as an example, I will discuss the expectations for new treatments that would be applied from animal models to humans.
Topics: Animals; Bronchopulmonary Dysplasia; Disease Models, Animal; Humans; Infant, Newborn; Infant, Premature; Lung; Mesenchymal Stem Cells
PubMed: 33465831
DOI: 10.1111/ped.14612 -
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