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Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 1. Ethics in Biomedical Animal Research: The Key Role of the Investigator

by Jerrold Tannenbaum

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128071915
  • Language : En, Es, Fr & De
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This chapter presents an overview of ethical principles that are essential for the proper conduct, and the continuing progress, of animal research aimed at understanding human disease. The chapter identifies fundamental principles of animal research ethics, and discusses ethical and empirical foundations of these principles. Guidelines are offered for applying these fundamental principles in the design and implementation of animal research projects. The chapter highlights several important ethical issues regarding which the biomedical research community has expressed lack of clarity or disagreement, and suggests considerations that are relevant for resolution of these issues. Recommendations are offered for participation by investigators in ethical discussion of their work, and of biomedical animal research generally. The general themes of the chapter are that investigators play the primary role in assuring the ethical conduct of biomedical animal research, and that a crucial foundation of ethical animal research is sound science.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 16. Animal Models of Bone Diseases-A

by Lixin Kan

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072067
  • Language : En, Es, Fr & De
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Bone disorders have a major impact on general population and cover a broad spectrum of diseases. At one end of the spectrum are the common disorders that are featured with age related progressive degeneration, and at the other end are the rare but serious congenital abnormities. Deeper understanding of the underlying mechanisms is a key to ensure the timely diagnosis, cost-effective prevention and treatment of these disorders. Animal models that could mimic the human pathologic conditions are tremendous helpers to achieve these goals, since clinical relevant animal models are essential to investigate disease states, test hypothesis, and screen drugs. This chapter tries to provide an overall view of the numerous animal models of important bone diseases, including osteoarthritis, osteoporosis and osteogenesis imperfecta, because these disorders are clinically important and also reflect the salient features of both extremes of bone disorders.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 38. Animal Models of Human Viral Diseases

by Sara I. Ruiz,Elizabeth E. Zumbrun,Aysegul Nalca

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072288
  • Language : En, Es, Fr & De
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As the threat of exposure to emerging and reemerging viruses within a naive population increases, it is vital that the basic mechanisms of pathogenesis and immune response be thoroughly investigated. By using animal models in this endeavor, the response to viruses can be studied in a more natural context to identify novel drug targets, and assess the efficacy and safety of new products. This is especially true in the advent of the Food and Drug Administration's animal rule. Although no one animal model is able to recapitulate all the aspects of human disease, understanding the current limitations allows for a more targeted experimental design. Important facets to be considered before an animal study are the route of challenge, species of animals, biomarkers of disease, and a humane endpoint. This chapter covers the current animal models for medically important human viruses, and demonstrates where the gaps in knowledge exist.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 33. Genetically Modified Animal Models

by Lucas M. Chaible,Denise Kinoshita,Marcus A. Finzi Corat,Maria L. Zaidan Dagli

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072237
  • Language : En, Es, Fr & De
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Genetically modified animals were created about 30 years ago, and are considered good models of human diseases. In this chapter, the types of genetically engineered mice, such as transgenic, knockout conditional knockout, and knockin animals, and the general techniques on how to obtain them are described. In addition, the available genetically modified models for genetic diseases, multifactorial and polygenic (complex) disorders, neurodegenerative, inflammatory diseases, besides cancer models, are presented. The aim of the chapter is to help investigators to find out the best models for their studies.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
A Book

by P. Michael Conn

  • Publisher : Academic Press
  • Release : 2017-06-20
  • Pages : 1198
  • ISBN : 0128096993
  • Language : En, Es, Fr & De
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Animal Models for the Study of Human Disease, Second Edition, provides needed information on model sharing, animal alternatives, animal ethics and access to databanks of models, bringing together common descriptions of models for busy researchers across biomedical and biological sciences. Offering easily searchable advantages and disadvantages for each animal model and organized by disease topics, this resource aids researchers in finding the best animal model for research in human disease. Organized by disease orientation for ease of searchability Provides information on locating resources, animal alternatives, and animal ethics Covers a broad range of animal models used in research for human disease Contributed by leading experts across the globe Expanded coverage of diabetes and neurological diseases

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 32. Genetically Tailored Pig Models for Translational Biomedical Research

by Bernhard Aigner,Barbara Kessler,Nikolai Klymiuk,Mayuko Kurome,Simone Renner,Annegret Wünsch,Eckhard Wolf

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072229
  • Language : En, Es, Fr & De
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Basic research of the pathobiology of diseases as well as of therapeutic strategies usually is carried out in rodents as animal models. Translational research that transfers novel results from basic research to clinical application often requires analyses in additional nonrodent models and/or large animal models that share specific pathophysiological characteristics with the human diseases in question. As prerequisites for the generation of appropriate disease models by genetic engineering, pigs exhibit suitable reproductive performance traits, pig genome analyses resulted in the availability of several resources of genomic data, and efficient and precise techniques for the genetic modification of pigs have been established. In the recent years, genetically engineered pigs were increasingly generated as biomedical research tools for specific human genetic diseases. Here, we review the current state of the techniques used for the production of genetically engineered pigs as well as the establishment of genetically engineered pigs as models for human diseases.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 37. Human Herpesviruses and Animal Models

by Alistair McGregor,K. Yeon Choi,Scott Schachtele,James Lokensgard

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 012807227X
  • Language : En, Es, Fr & De
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This chapter reviews the various human herpesviruses (HHVs) and their associated diseases. Animal models have been developed to study some HHVs, and these, as well as development of intervention strategies using these models, are discussed. Additionally, specific protocols are included to enable investigators to use the current state of the art techniques to explore various aspects of viral infection in animal models. The protocols presented in this chapter are a collection of techniques that are generally applicable to the study of all herpesviruses in animal models and can be utilized by both the experienced and inexperienced virologist.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 8. Animal Models for Cardiovascular Research

by Li Chen,Richard P. Shannon,You-Tang Shen

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128071982
  • Language : En, Es, Fr & De
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With advances in molecular and genomic research offering novel insights into cardiovascular diseases, many transgenic animal models have been recently developed and characterized. Currently, more than 90 percent of all laboratory animal experiments are conducted in mice and rats. Although there are many scientific advantages to using small animal models, it has been recently recognized that many exciting therapeutic targets identified in small animals are not validated in clinical trials in patients. Thus, suitable large animal models, particularly under conscious state with appropriate direct measurements of cardiovascular function, are needed to serve as a better translational bridge between preclinical and clinical studies. In this chapter, we primarily focus on surgically instrumented large animal models of common cardiovascular disease studied in the conscious state. In addition, several important physiological factors that influence the characteristics of the models, as well as the importance of proper data interpretation, will also be discussed.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 10. Models for the Study of Atherosclerosis and Thrombosis

by Lina Badimon,Laura Casani,Gemma Vilahur

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072008
  • Language : En, Es, Fr & De
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Experimental approaches to understand the pathophysiology of atherosclerosis and thrombosis involve the combination of both cellular and animal approaches. Animals have been instrumental in biomedical research in order to provide a better understanding on the mechanisms that have already been outlined in in vitro studies. Atherosclerosis studies were firstly carried out in rodents using diet-induced atherosclerosis approaches. However, these diets were un-physiological and the developed lesions were often limited in size, composition, and location largely differing from humans. During the last years, with the advent of molecular genetics and genetic manipulation techniques, the development of gene-engineered animals has allowed an explosion in the number of models resulting in a tremendous progress in the understanding of both atherosclerosis and thrombosis. However, direct translation from rodents to humans has to be taken with caution because of the well-reported species-related differences. Although there is no known animal model for human disease, large animal models have demonstrated better suitability for translation to humans. For instance swine, a species that spontaneously develops atherosclerosis and thrombosis, are more closely mimics of the macrovascular-related thrombotic complications found in humans. This book chapter provides an in depth overview of the currently available small and large animal modelsof atherosclerosis and thrombosis and examinestheir applicability for translational research purposes as well as highlights species-related differences with humans.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 27. The Importance of Olfactory and Motor Endpoints for Zebrafish Models of Neurodegenerative Disease

by Angela L. Shamchuk,Keith B. Tierney

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072172
  • Language : En, Es, Fr & De
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Olfactory dysfunction, although caused by many factors including physical damage and genetic abnormalities, is an early stage symptom of several neurodegenerative diseases. Not only is the olfactory system subject to the specific histological abnormalities but patients also lose the capacities to detect, identify, and discriminate among odors. In addition to olfactory deficits, motor dysfunction is another prominent manifestation of these conditions. Recent studies have begun to create zebrafish (Danio rerio) models for neurodegenerative diseases. Despite successful execution, there remains a great deal of potential in testing the models using established methods of olfactory and motion assessment. This chapter discusses the current zebrafish models and suggests olfactory and motor endpoints for Parkinson's, Alzheimer's, Huntington's, multiple system atrophy, and amyotrophic lateral sclerosis.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 29. Animal Models of Reward Behavior

by Charles W. Schindler,Steven R. Goldberg

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072199
  • Language : En, Es, Fr & De
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Reward behavior represents a subset of conditioning procedures that have been developed by psychologists to study learning in animals. In particular, rewarded behavior involves an instrumental response that is maintained by a reinforcer. The procedures that have been developed cover a broad spectrum of behaviors, from simple running in a straight alley to very complex operant schedules of reinforcement that can require multiple responses over long periods of time. Many species of animal have also been trained on these procedures. Procedures have been developed to study the initial learning process as well as steady-state behavior. Procedures have also been developed to study memory. As such, rewarded behavior models can be used to study a wide variety of human diseases and conditions, such as Alzheimer's disease, obesity, drug abuse, obsessive-compulsive disorder and many others.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 35. Animal Models for the Study of Infection-Associated Preterm Birth

by Matthew W. Kemp,Gabrielle C. Musk,Masatoshi Saito

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072253
  • Language : En, Es, Fr & De
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In industrialized and developing countries, preterm birth (live delivery before 39 weeks of gestation) is both a leading cause of neonatal death and a major risk factor for respiratory, neurological, and cognitive disabilities in those infants who survive to adolescence. Intrauterine infection is considered a leading cause of preterm birth; data from clinical and experimental studies suggest that in utero infection accounts for upward of 40% of preterm deliveries. This chapter is written with two aims: the first is to provide the reader with an introduction to infection-associated preterm birth, highlighting the importance of animal-based studies in the development of this field; and the second, adopting a practical focus, is designed to provide the reader with technical insight into the use of sheep as a model organism for the study of fetal inflammatory responses to the presence of microbial agonist in the uterine sphere.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 26. Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Animal Models for Parkinson's Disease

by Jiro Kasahara,Mohammed Emamussalehin Choudhury,Hironori Yokoyama,Naoto Kadoguchi,Masahiro Nomoto

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072164
  • Language : En, Es, Fr & De
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Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a slowly progressive motor dysfunction and loss of dopaminergic neurons located in the substantia nigra innervating the striatum, causing depletion of dopamine, which leads to a hyperactivation of the striatal medial spiny neurons. To understand the pathophysiological details of PD and for developing and screening the novel therapeutic and/or neuroprotective substances, animal models for PD induced by neurotoxins have been developed. Among them, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the most commonly used since it causes a selective loss of dopaminergic neurons in the substantia nigra and induces typical PD-like symptoms both in human and in experimental animals with a relatively simple application. In this chapter, we first overview the characteristics of PD and animal models with neurotoxins to establish, then focus on, MPTP-treated mouse and common marmoset models for PD with their practical experimental protocols and applications.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 15. Animal Models of Cholestasis

by Peter Fickert,Marion J. Pollheimer,Christoph H. Österreicher,Michael Trauner

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072059
  • Language : En, Es, Fr & De
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Cholestatic liver diseases, such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC), represent an important group of liver diseases of the intra- and extrahepatic bile ducts frequently causing end-stage liver disease with significant morbidity and mortality due to limited treatment options. The limitations of the currently available medical therapy largely reflect our deficits in understanding the pathophysiology of cholestatic liver diseases. Therefore, there is an urgent need for reliable, well-defined and easily reproducible animal models to gain insights into the PSC and PBC pathophysiology and to test novel treatment modalities. We aimed to provide a systematic overview of currently available animal models for sclerosing cholangitis and biliary fibrosis and critically discuss the characteristics of rodent models for PSC and PBC, models of experimental biliary obstruction, models of inflammation-induced cholestasis, as well as models of inherited cholestatic syndromes.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 34. Mouse Models for Human Diseases by Forward and Reverse Genetics

by Yoichi Gondo

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072245
  • Language : En, Es, Fr & De
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To create and establish mutant mice as models for human diseases and traits, various forward and reverse genetics tools are currently available. Newly developed tools of high-throughput identification of novel mutations and site-directed mutagenesis, or gene targeting, in the mouse genome have caused forward and reverse genetics, respectively, to rapidly expand during the last two decades. Worldwide efforts including a variety of international consortiums have been producing many useful mutant mouse strains for functional genomics to elucidate the mechanisms behind diseases and traits. Resource centers and public databases have also been built to enhance their utilities. The modeling has started from Mendelian monogenic traits and has expanded to more complex quantitative traits as well. Multidisciplinary integration among, for example, molecular, cellular, and developmental biology; genetics; genomics; medicine; statistics; and informatics must be orchestrated to fully utilize the resources and knowledge of model mice.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 19. Animal Models of Fibrosis in Human Disease

by Gideon P. Smith

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072091
  • Language : En, Es, Fr & De
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Although fibrosis can occur as part of normal wound healing, dysregulated fibrosis can affect almost any organ and results in severe dysfunction. Despite the variety of human disease of which this is a feature these diseases remain poorly understood due in part to the slow largely asymptomatic onset. Animal models are our only means to examine the early stages of these diseases. With them we can isolate perturbations in signaling pathways, chemokines and cytokines and study their effects. Here we summarize animal models that have been developed for the study of the most common human fibrotic conditions. We separate models of scleroderma and cirrhosis as the model development for each of these conditions face unique challenges. Although still imperfect, elegant solutions have been developed for modeling fibrosis in each. Indeed, progress in this area is currently rapid, and animal models will likely remain critical in moving forward our scientific understanding of these disease states.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 23. Animal Models of Stroke Versus Clinical Stroke: Comparison of Infarct Size, Cause, Location, Study Design, and Efficacy of Experimental Therapies

by Victoria E. O’Collins,Geoffrey A. Donnan,Malcolm R. Macleod,David W. Howells

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 012807213X
  • Language : En, Es, Fr & De
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A quantitative and qualitative comparison of contemporary neuroprotection and thrombolytic stroke trials and their preclinical animal counterparts has been undertaken, with meta-analysis (DerSimonian and Laird, 1986) used to evaluate imaging and histological outcomes. Results from 35 clinical trials including 5,532 patients were compared with data from 3,145 pre-clinical acute-stroke experiments in 45,476 animals. While clinical trials tended to be of higher methodological quality and have larger sample sizes than animal experiments (71 patients vs. 7 animals per group), both were similarly underpowered owing to the greater variability in human stroke (average standard deviation of mean in humans 99% v 30% in animals). Proportionally, animal infarcts were almost four times larger than human infarcts in untreated control groups (27% v 8% of the hemisphere) although there was considerable variability in size owing to comorbidities and stroke type. Eighty-six percent of animal studies and 54% of clinical trials reported smaller infarcts in groups receiving treatment, with 41% of clinical trials reporting an improvement in the pre-specified hypothesis. Animal experiments were not effective in predicting individual trial results, nor the level of neuroprotection, however, there was a fair agreement between the direction of the animal and clinical outcomes when looking at the overall direction of drug outcome. As a drug screening tool, experimental stroke studies need refinement. Rational frameworks for translational research will help.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 42. Animal Models for the Study of Multiple Sclerosis

by Robert H. Miller,Sharyl Fyffe-Maricich,Andrew V. Caprariello

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072326
  • Language : En, Es, Fr & De
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The most common demyelinating disease of the central nervous system (CNS) in the young adult population is multiple sclerosis (MS). MS is characterized by the focal loss of myelin sheaths in the brain and in the spinal cord of patients that is correlated with elevated activity of the immune system directed toward CNS antigens including myelin. The progression of MS is highly variable, but in many cases, it is characterized by a series of relapsing and remitting attacks that slowly increase residual functional deficit. Often, after several years, the disease transitions to a more progressive phenotype. Much of what is known about the pathology of MS is derived from a number of animal models. The most common animal model for the study of MS is experimental allergic encephalitis (EAE), which depending upon the host animal can present as relapsing/remitting or progressive disease. Although EAE has provided mechanistic insights implicating T-cell activation in the onset and progression of disease, understanding the mechanisms of pathology onset and myelin repair in the CNS require alternative models. One emerging hypothesis is that activation of T cells is secondary to pathogenesis of oligodendrocytes and animals models in which targeted loss of oligodendrocytes are beginning to reveal an understanding of the initiation of CNS demyelination. Myelin repair is difficult to study in the setting of EAE or oligodendrocyte pathogenesis; however, toxin models that result in localized demyelination as a consequence of direct injection or oral delivery have provided critical insights into cells of origin, timing, and molecular mechanisms guiding remyelination. Taken together, these three distinct model systems provide a strong basis for dissecting cell and molecular mechanism of demyelination as well as characterizing the efficacy of targeted therapeutics.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 17. Animal Models of Bone Disease-B

by Meghan E. McGee-Lawrence,Frank J. Secreto,Farhan A. Syed

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072075
  • Language : En, Es, Fr & De
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The skeleton is a multifunctional organ system that serves several vital roles in the body. Although bone has the ability to remodel itself to repair damage and respond to calcium demands, it is subject to the rigors of aging, hormonal changes, and environment. Understanding the mechanisms that cause bone loss is an important facet of human medicine. Animal models permit mechanistic study of processes that regulate development and maintenance of skeletal mass, enabling meticulous investigation of new orthopedic strategies or bone-targeted pharmacologic therapies. The selection of an appropriate animal model, choice of skeletal analysis techniques, and proper interpretation of data are vital components of experimental design and analysis in bone research. In this chapter, we review time-tested criteria for choosing appropriate animal models, describe several common animal models of osteoporosis, and summarize some of the basic methodology available for in vivo, ex vivo and in vitro analysis of skeletal biology.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease
Chapter 11. Animal Models of Metabolic Syndrome

by Heather A. Lawson

  • Publisher : Elsevier Inc. Chapters
  • Release : 2013-05-29
  • Pages : 1108
  • ISBN : 0128072016
  • Language : En, Es, Fr & De
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Metabolic syndrome (MetS) is a clustering of metabolic complications representing a pre-morbid condition that is a substantial public health burden. Animal models provide an opportunity to examine correlations among different metabolic parameters to understand why metabolic complications sometimes cluster and sometimes do not. This chapter provides an overview of animal models of MetS that are used to understand etiology and pathophysiology, with a focus on methods of identifying and testing candidate genes with the aim of translating results to human studies. Genetic, epigenetic, environmental, and gene by environmental methods and results are discussed along with important lessons learned. Rodent models are the most frequently used, however other animal models including dogs, pigs, sheep, and non-human primates have contributed to our understanding of MetS and each are discussed. Additionally, animal models used to test physiological hypotheses are reviewed along with their potential to illuminate DNA sequence–metabolic function relationships to inform therapies.