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Animal Models For The Study Of Human Disease

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Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : P. Michael Conn
Publisher : Academic Press
Release : 2017-06-20
ISBN : 0128096993
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Daniel Butzke,Barbara Grune,Josephine Kugler,Michael Oelgeschläger,Andrea Seiler,Dana Sittner,Manfred Liebsch,Andreas Luch
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128071931
Language : En, Es, Fr & De

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Book Description :

The first years of the 21st century have seen an unparalleled progress in biomedical sciences. Several dogmata that haunted scientific debate for decades were easily abandoned, and there is a fundamental shift away from eminence-based toward evidence-based assessment of preclinical models, probing their true value in predicting clinical outcomes of human diseases. Likewise, several new approaches, e.g., stem cell-based, diseases-in-a-dish and organs-on-a-chip and lab-on-a-chip technologies have revitalized the domain of alternatives to animal experimentation. In our review, we portray these and other efforts to bring forth relevant and ethically inoffensive models of human diseases.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Judith Axler Turner
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128071923
Language : En, Es, Fr & De

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Book Description :

Identifying and selecting the most appropriate animal model is a challenge, but the U.S. Federal Government’s National Institutes of Health, has supported several efforts to make the job of finding disease models easier. These efforts began with support for databases about specific species, and have graduated to support for discipline-specific studies and cross-species resources. This article tracks LAMHDI, the initiative to Link Animal Models to Human DIsease (www.lamhdi.org), which brings together data about five species: flies, mice, rats, yeast, and zebrafish, and allows scientists to search across these data, principally by disease and gene. This chapter explains how LAMHDI was conceived, and where LAMHDI hopes to go in moving into phenotypical as well as genotypical data through networks and visualization.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Robert H. Miller,Sharyl Fyffe-Maricich,Andrew V. Caprariello
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072326
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Lucas M. Chaible,Denise Kinoshita,Marcus A. Finzi Corat,Maria L. Zaidan Dagli
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072237
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Jerrold Tannenbaum
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128071915
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Yoichi Gondo
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072245
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Gideon P. Smith
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072091
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Ross A. Breckenridge
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128071974
Language : En, Es, Fr & De

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Book Description :

Myocardial disease is one of the largest medical burdens facing populations of the developed world. Increasing diabetes and obesity in both the developed and developing world suggests that this problem will increase with time. So far, development of novel therapeutic approaches to myocardial disease has lagged behind medical need. One of the key components lacking from this area of medicine is reliable animal systems to model increasingly complex patient populations. This chapter takes a disease-centred approach to reviewing commonly used animal models of myocardial disease. It goes on to discuss possible future approaches to adapting existing models to the changing spectrum of cardiac disease.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Charles W. Schindler,Steven R. Goldberg
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072199
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Jitka Sviglerova,Jitka Kuncova,Milan Stengl
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128071990
Language : En, Es, Fr & De

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Book Description :

Impairment, altered function or altered requirements of various organs lead to corresponding changes of cardiovascular system, especially its central organ, the heart. The heart adapts to the altered conditions and requirements by intensive remodeling. The remodeling is usually very complex, including both structural (e.g. hypertrophy, fibrosis) and functional (e.g. electrophysiological, contractile remodeling) changes. The remodeling is initially compensatory and beneficial optimizing the pumping function but gradually it may become detrimental (heart failure, life-threatening arrhythmias). In this chapter we have focused on three experimental models, in which the heart is not targeted primarily, however the primary disease eventually affects the cardiovascular system significantly: diabetes mellitus, renal failure, and dysfunctional autonomic innervation. Rat models of these three conditions are described in detail with special focus on methodological aspects and experimental results obtained in our laboratory.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Jiro Kasahara,Mohammed Emamussalehin Choudhury,Hironori Yokoyama,Naoto Kadoguchi,Masahiro Nomoto
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072164
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Sara I. Ruiz,Elizabeth E. Zumbrun,Aysegul Nalca
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072288
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Matthew W. Kemp,Gabrielle C. Musk,Masatoshi Saito
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072253
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Heather A. Lawson
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072016
Language : En, Es, Fr & De

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Book Description :

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.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Lina Badimon,Laura Casani,Gemma Vilahur
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072008
Language : En, Es, Fr & De

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Book Description :

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 Book
Author : Mengqi Chen,Doris Kretzschmar,Giuseppe Verdile,Michael Lardelli
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072156
Language : En, Es, Fr & De

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Book Description :

Alzheimer’s disease (AD) is a major and increasing burden on families, communities, and national health budgets. Despite intensive and extended research, there is still widespread debate about its cause(s), and no effective treatments exist. Familial (inherited, mainly early onset) and sporadic (mainly late onset) forms of the disease exist, and it is uncertain to what extent they are related. Transgenic mouse models have dominated the investigation of this disease, but their validity can be questioned. Numerous alternative models exist that can provide valuable information on the molecular and cellular basis of AD. In this chapter, we review the various invertebrate, nonmammalian vertebrate, and mammalian models and how these have been used to investigate this disease. We examine the strengths and weaknesses of these various model systems. Of course, animal models never completely reflect the true nature of a human disease, but progress in understanding and finding preventative and ameliorative treatments for AD is hindered by the lack of a convincing hypothesis for the cause of this complex condition.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Toshiyuki Yamamoto
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072318
Language : En, Es, Fr & De

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Book Description :

Systemic sclerosis (scleroderma) is a fibrotic condition characterized by immunologic abnormalities, vascular injury, and increased accumulation of extracellular matrix (ECM) proteins in the affected organs. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that ECM overproduction by activated fibroblasts results from a complex interaction among endothelial cells, immunocytes, and fibroblasts, involving a number of mediators such as cytokines, chemokines, growth factors, and their receptors. For a better understanding of the pathophysiology of scleroderma, animal models are important tools. They reproduce several histological and biochemical aspects resembling human scleroderma, and we can obtain lots of new findings through animal studies. On the other hand, it must be emphasized that there are no animal models so far exhibiting all the aspects of human scleroderma, and studying animal models cannot answer all the problems of human scleroderma. This chapter introduces the current concepts of various animal models for scleroderma, and discusses their advantages/disadvantages, contribution to our understanding of the pathogenesis, and therapeutic approach for human scleroderma.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Caroline J. Zeiss
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128071958
Language : En, Es, Fr & De

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Book Description :

Age-related macular degeneration (AMD) is a degenerative condition that begins in Bruch’s membrane and progresses to involve the retinal pigment epithelium and ultimately, overlying photoreceptors. The only required etiologic factor is age, and AMD is regarded as the leading cause of blindness in individuals over 65 years. AMD results from variable contributions of age, environment, and genetic predisposition. Many loci are linked to AMD—in the vast majority of cases, the disease is associated with polymorphisms within these genes, rather than mutations that ablate gene function. The etiologic complexity of AMD is reflected by the paucity of animal models that entirely replicate the human disease. In this review, we compare the salient anatomy of the primate and rodent retina, particularly in the light of AMD pathology. Next, prevailing hypotheses explaining how AMD may develop are discussed. These include the role of complement activation and macrophage chemotaxis in AMD, molecular mechanisms of choroidal neovascularization, and the roles of oxidative damage and lipid metabolism. An overview of spontaneous and induced non-human primate models is given, and relevant mouse models are described in the context of each pathogenetic mechanism.

Animal Models for the Study of Human Disease

Animal Models for the Study of Human Disease Book
Author : Joachim Wistuba,Steffi Werler,Lars Lewejohann
Publisher : Elsevier Inc. Chapters
Release : 2013-05-29
ISBN : 0128072210
Language : En, Es, Fr & De

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Book Description :

Klinefelter syndrome (KS) is a frequent (0.2%) sex chromosomal disorder in males presenting with a 47,XXY karyotype. This condition is associated with infertility, hypogonadism, and metabolic and cognitive impairments. As experimental research is restrictive in patients, animal models for KS are needed to explore its molecular and genetic basis. Supernumerary X chromosomes due to meiotic nondisjunctions sporadically also occur in males of other mammalian species and provoke the same or at least some of the features observed in patients. However, as the condition is linked to infertility, the generation and availability of a substantial number of experimental animals cannot be fulfilled using individuals with the naturally occurring syndrome. Breeding of B6Ei.Lt-Y∗ mice carrying a mutated Y chromosome provides a sufficient number of males with a supernumerary X chromosome that resembles the human disorder and permits the design and performance of the complex investigations needed to elucidate the mechanisms at the heart of the pathology. This chapter reviews the insights obtained into studies into KS over the past decades and highlights the contribution made by the animal model.