scholarly journals Mouse models of human disease: Identification of animal models for translational research

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S18-S19
Author(s):  
Cynthia Smith
2008 ◽  
Author(s):  
Martin Fenner

One of the opening lectures this Saturday of the International Congress of Genetics was held by Mario Capecchi. His talked was entitled Modeling human disease in the mouse: from cancer to neuropsychiatric disorders. In the first half he described his mouse model of synovial sarcoma. ...


2021 ◽  
Vol 15 (1) ◽  
pp. 8
Author(s):  
Rahman Ladak ◽  
Dana Philpott

With growing evidence that human disease is affected by the microbiota, many researchers have sought to modulate the microbiomes of mice to improve translational research. Altering their microbiomes, which are usually germ-free or specific pathogen-free, might allow mice to more accurately model human disease and hence produce more applicable findings. However, this has been difficult to apply to individual projects due to the disparity of explained methods and results. In this review, we first describe the immunological functions of the gut microbiota and the methods of altering mice microbiota, from transplantation route to age of transplantation to microbiota source. We then present an approach for how the gut microbiota might be considered when modelling human disease in mice. By organizing findings by type of disease - neurological, immunological, chronic inflammatory, and cancer - we propose that mouse models can be improved by considering the source of the microbiota, the presence or absence of certain microbial phyla, and by timing the transplantation during a physiologically relevant stage of development, such as the first five weeks of life.


2013 ◽  
Vol 10 (5) ◽  
pp. 373-374 ◽  
Author(s):  
Amanda M Burkhardt ◽  
Albert Zlotnik

2018 ◽  
Vol 72 ◽  
pp. 1032-1042 ◽  
Author(s):  
Natalia Dzięgiel ◽  
Paulina Szczurek ◽  
Jacek Jura ◽  
Marek Pieszka

The advances in translational biomedical research, especially in genetic engineering, created new opportunities to trace the courses of human diseases and develop effective therapeutic methods. There remains, however, a growing demand for appropriate animal models for the precise evaluation of the efficacy and safety of new drugs or therapeutic concepts. Thus far, rodent models have been most widely used in translational research; however, since they do not perfectly reflect the human disease phenotype, transgenic pigs are increasingly being utilized as animal models. Thanks to the anatomical and physiological similarities between pigs and humans, swine are considered to be one of the most valuable animal models used in preclinical studies, including nutritional, metabolic and cardiovascular research. The resemblances involve the gastrointestinal, cardiovascular, urinary, respiratory, skeletal muscle and immune systems, as wells as body size, body composition and the omnivorous food choice. In addition, pigs are characterized by high fertility and fecundity, as well as the ease of use and low maintenance costs. Importantly, the existing efficient genetic engineering techniques enable relatively easy generation of tailored porcine models of human disease. One should be aware, however, of some physiological differences between humans and pigs to correctly interpret induced toxicological changes. The article provides an overview of current techniques for genetic modification of pigs, as well as the use of swine models in translational research exemplified by xenotransplantation, metabolic and coronary heart disease, and the gastrointestinal motility studies.


ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 40-50
Author(s):  
Sue E Knoblaugh ◽  
Tobias M Hohl ◽  
Krista M D La Perle

Abstract Over 60% of NIH extramural funding involves animal models, and approximately 80% to 90% of these are mouse models of human disease. It is critical to translational research that animal models are accurately characterized and validated as models of human disease. Pathology analysis, including histopathology, is essential to animal model studies by providing morphologic context to in vivo, molecular, and biochemical data; however, there are many considerations when incorporating pathology endpoints into an animal study. Mice, and in particular genetically modified models, present unique considerations because these modifications are affected by background strain genetics, husbandry, and experimental conditions. Comparative pathologists recognize normal pathobiology and unique phenotypes that animals, including genetically modified models, may present. Beyond pathology, comparative pathologists with research experience offer expertise in animal model development, experimental design, optimal specimen collection and handling, data interpretation, and reporting. Critical pathology considerations in the design and use of translational studies involving animals are discussed, with an emphasis on mouse models.


2021 ◽  
Author(s):  
Aaron C. Ericsson ◽  
Craig L. Franklin

AbstractJust as the gut microbiota (GM) is now recognized as an integral mediator of environmental influences on human physiology, susceptibility to disease, and response to pharmacological intervention, so too does the GM of laboratory mice affect the phenotype of research using mouse models. Multiple experimental factors have been shown to affect the composition of the GM in research mice, as well as the model phenotype, suggesting that the GM represents a major component in experimental reproducibility. Moreover, several recent studies suggest that manipulation of the GM of laboratory mice can substantially improve the predictive power or translatability of data generated in mouse models to the human conditions under investigation. This review provides readers with information related to these various factors and practices, and recommendations regarding methods by which issues with poor reproducibility or translatability can be transformed into discoveries.


2021 ◽  
Vol 9 (5) ◽  
pp. 1062
Author(s):  
Chunye Zhang ◽  
Craig L. Franklin ◽  
Aaron C. Ericsson

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.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker

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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