Animal Models for the Study of Human Disease
1st Edition
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Description
Animal Models for the Study of Human Disease identifies important animal models and assesses the advantages and disadvantages of each model for the study of human disease. The first section addresses how to locate resources, animal alternatives, animal ethics and related issues, much needed information for researchers across the biological sciences and biomedicine.The next sections of the work offers models for disease-oriented topics, including cardiac and pulmonary diseases, aging, infectious diseases, obesity, diabetes, neurological diseases, joint diseases, visual disorders, cancer, hypertension, genetic diseases, and diseases of abuse.
Key Features
- 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
Readership
Biomedical and basic science researchers, graduate students and postdocs.
Table of Contents
Preface
List of Contributors
Part I: Ethics, Resources and Approaches
Chapter 1. Ethics in Biomedical Animal Research: The Key Role of the Investigator
Nature and Scope of the Chapter
The Subject Matter of Animal Research Ethics
Aspects of Animal Use and Care Relevant to Animal Research Ethics
Why Investigators are Uniquely Qualified to Engage in Ethical Assessment of Animal Research
Why Investigators Should Commit Themselves to Ethical Conduct of Animal Research
Why Investigators Play the Key Role in Assuring the Ethical Conduct of Animal Research Projects
Sources of Support and Guidance in Conducting Ethical Research
Developing Useful Ethical Guidelines
Fundamental Principles of Animal Research Ethics
Practical Ethical Guidelines for Investigators
Some Current Difficult Issues in Animal Research Ethics
General Suggestions for Investigators
References
Chapter 2. Access to Resources: A Model Organism Database for Humans
Acknowledgments
The Problem
The LAMHDI Solution
The Ideal Solution
References
Chapter 3. The Advent of the Golden Era of Animal Alternatives
Introduction
Analytical Tools for the Detection of Food-Borne Disease
An in Vitro System to Assess Adverse Effects During Development
Diseases-in-a-dish
Noninvasive Imaging and Recording
Conclusions
References
Chapter 4. Environmental Enrichment for Animals Used in Research
Acknowledgments
Introduction
Applied Science: Enrichment as a Welfare Tool
Basic Science: Enrichment and Animal Models
Enrichment and Experimental Variability
Environmental Enrichment Regulations
Implementing an Enrichment Plan
Conclusions
References
Part II: Vision
Chapter 5. Animal Models of Age-Related Macular Degeneration
Introduction
Comparative Retinal Anatomy and the Pathology of AMD
The Genetics of AMD
Inflammation in AMD
HTRA1 and LOC387715/ARMS2 in AMD
Oxidative Damage and AMD
Lipid Metabolism and AMD
Spontaneously Occurring Primate Models of AMD
Modeling Choroidal Neovascularization in Advanced AMD
Conclusion
References
Chapter 6. N-Methyl-N-Nitrosourea Animal Models for Retinitis Pigmentosa
Acknowledgments
Introduction
Time-Course Progression of MNU-Induced Retinal Degeneration
Retinal Degeneration Caused by MNU in Various Animal Species
Age-Related Photoreceptor Cell Damage and Sensitivity to MNU
Photoreceptor Cell Death, Cell Debris Removal, and RPE Cell Migration
Molecular Mechanisms in Photoreceptor Cell Death Caused by MNU
Therapeutic Trials Against MNU-Induced Photoreceptor Apoptosis
Concluding Remarks
References
Part III: Cardiac and Cardiovascular
Chapter 7. Animal Models of Myocardial Disease
Introduction
The Spectrum of Cardiovascular Disease
Choice of Animal System
Experimental Design
Ischemic Heart Disease
Systolic Heart Failure
Diastolic Heart Failure
Infective Myocarditis
Cardiomyopathies
Diabetes and Obesity-Related Heart Disease
The Future of Animal Models for Cardiovascular Disease
References
Chapter 8. Animal Models for Cardiovascular Research
Introduction
Myocardial Ischemic Models
Hypertension and Left Ventricular Hypertrophy Models
Heart Failure Models
Cardiovascular Denervation Models
Future Directions
References
Chapter 9. Cardiovascular Models: Heart Secondarily Affected by Disease
Acknowledgment
Introduction
The Heart and Diabetes Mellitus
The Heart and Renal Failure
The Heart and Dysfunctional Sympathetic Innervation
References
Chapter 10. Models for the Study of Atherosclerosis and Thrombosis
Acknowledgments
Small Versus Large: Size Matters?
Atherosclerosis
Thrombosis
Animal Models of Von Willebrand Disease
Animal Models of Venous Thrombosis
Animal Models of Plaque Rupture
Conclusions and Future Perspectives
References
Part IV: Obesity, Metabolic and Liver
Chapter 11. Animal Models of Metabolic Syndrome
Introduction and Overview
Choosing an Animal Model of MetS
Animal Models of MetS Etiology
Genetic Factors
Environmental Factors
Animal Models of MetS Pathophysiology
Conclusions
References
Chapter 12. Invertebrates in Obesity Research: A Worm’s Perspective
Obesity Worldwide
Model Organisms
Introducing the Nematode C. elegans
Lipids in C. elegans
C. elegans as a Model for Obesity Research
Fat Pathways in Mammals and Worms
Obesity in Humans and Model Organisms: A Genomic Approach
The Link Between Fat Metabolism and Other Diseases
Other Invertebrate Models in Obesity Research
Conclusion
References
Chapter 13. Animal Models of Dietary-Induced Obesity
Acknowledgments
Usefulness of Animal Models of Human Obesity
Fat-Rich Diets
Physiological Mechanisms of Fat-Rich-Diet-Induced Obesity
Behavioral Mechanisms of Dietary Obesity
Reversal of Dietary Obesity
Conclusions
References
Chapter 14. Animal Models for Manipulation of Thermogenesis
Introduction
Brown Fat
BAT and Thermogenesis in White Adipose Tissue
“Browning” of White Adipose Tissue
Skeletal Muscle
Models of Obesity
Diet-Induced Obesity and Thermogenesis
Photoperiod and Seasonality as Models of Metabolic Function
Fetal Growth Retardation and Effect on Metabolic Balance
Transgenerational Effects of Obesity
Polygenic Models of Obesity
Concluding Remarks
References
Chapter 15. Animal Models of Cholestasis
Introduction
General Concepts of Normal Bile Formation
Liver Fibrosis in Cholestatic Liver Diseases
Models for (Primary) Sclerosing Cholangitis
Models for Primary Biliary Cirrhosis
Obstructive Cholestasis
Drug-Induced Cholestasis
Inflammation-Induced Cholestasis
Biliary Atresia
Inherited Cholestatic Syndromes
Summary and Conclusions
References
Part V: Bone and Skin
Chapter 16. Animal Models of Bone Diseases-A
Acknowledgments
Introduction
Animal Models of Age-Dependent Degenerative Bone Disorders
Animal Models of Congenital Bone Disorders
Conclusions
References
Chapter 17. Animal Models of Bone Disease-B
Acknowledgments
Introduction
Criteria for Choosing Animal Models for Bone Loss and Regeneration
Common Animal Models for Skeletal Research
Genetic Mouse Models for Elucidating Mechanistic Changes
Methods Used in Evaluating Bone Structure and Strength in Animal Models
In Vitro Models of Skeletal Biology
Conclusion and Closing Remarks
References
Chapter 18. Animal Models for Implant-Associated Osteomyelitis
Acknowledgments
Introduction
General Features of Osteomyelitis Animal Models
Rabbit Osteomyelitis Models
Rat Osteomyelitis Models
Mouse Models of Osteomyelitis
Large-Animal Models of Osteomyelitis
Areas for Improvement of Animal Models of Osteomyelitis
Biomarkers of Infection
Conclusion
References
Chapter 19. Animal Models of Fibrosis in Human Disease
Introduction
Animal Models of Fibrosis in Scleroderma
Conclusions
Liver Fibrosis
Conclusions
References
Part VI: Urinary Tract, Kidney and Bowel
Chapter 20. Animal Models of Lower Urinary Tract Dysfunction
The Requirement for Animal Models
The Normal Urinary Tract
Aging Animal Models
Bladder Outflow Tract Obstruction
Stress Urinary Incontinence
Bladder Pain Syndrome
Lower Urinary Tract Disorders of Neurological Origin
Animal Models of Central Nervous System Control Over Bladder Function
Diabetes and Lower Urinary Tract Dysfunction
Urinary Tract Infections
Congenital Anomalies
Tissue Engineering and the Urinary Tract
References
Chapter 21. Animal Models of Calcium Oxalate Kidney Stone Formation
Introduction
Calcium Oxalate Crystal Deposition in Rats
Calcium Oxalate Crystal Deposition in Mice
Calcium Oxalate Crystal Deposition in Pigs
Calcium Phosphate Crystal Deposition in Rats
Calcium Phosphate Crystal Deposition in Mice
Calcium Oxalate/Calcium Phosphate Association in Animal Models
Foreign-Body Stones
Comparison Between Rat and Human Nephrolithiasis
Concluding Remarks
References
Chapter 22. Animal Models of Inflammatory Bowel Disease for Drug Discovery
Acknowledgments
Introduction
Classification of Mouse IBD Models
Etiology and Mouse IBD Models
Classical Therapy and IBD Models
Biological Therapy and IBD Models
Conclusion
References
Part VII: The Brain, Stroke, and Neuromuscular
Chapter 23. Animal Models of Stroke Versus Clinical Stroke: Comparison of Infarct Size, Cause, Location, Study Design, and Efficacy of Experimental Therapies
Acknowledgments
Introduction
Systematic Review and Meta-Analysis Method
Results
Discussion
Conclusion
References
Chapter 24. Animal Models and Methods to Study the Relationships Between Brain and Tissues in Metabolic Regulation
Introduction
General Considerations
Technical Means to Investigate the Role of the Central Nervous System
Modulating Central Nervous System Activity
Study of Cerebral Responses
Behavioral and Metabolic Responses
Conclusion
References
Chapter 25. Models of Alzheimer’s Disease
Introduction
Invertebrate Models
Nonmammalian Vertebrates
Mammalian Models
Conclusions
References
Chapter 26. Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Animal Models for Parkinson’s Disease
Acknowledgment
Abbreviations
Introduction
Clinical Characteristics of PD and Their Relevant Symptoms in Animal Models
Molecular Pathophysiology of PD
Neurotoxins for Making PD Models
MPTP-Induced Mouse Model for PD
MPTP-Induced Common Marmoset Model for PD
Concluding Remarks
References
Chapter 27. The Importance of Olfactory and Motor Endpoints for Zebrafish Models of Neurodegenerative Disease
Introduction
Building Relevant Models
Olfactory–Neuromuscular Diseases
Conclusions
References
Part VIII: Behavior
Chapter 28. Animal Models of Drug Abuse: Place and Taste Conditioning
Acknowledgments
What is Drug Addiction and why Should we Study it?
Reward and Reinforcement
Aversive Drug Effects
The Place-Conditioning Procedure
The Flavor-Conditioning Procedure
Conclusion
References
Chapter 29. Animal Models of Reward Behavior
Acknowledgment
Reward Behavior
Examples of Reward Learning
What can be a Reward?
Factors Affecting Conditioning with Rewards
Role of Pavlovian Conditioning in Reward Learning
Conclusion
References
Chapter 30. Modeling Schizophrenia in Animals
Overview of Schizophrenia
Approaches to Creating Animal Models with Relevance to Schizophrenia
Features of Schizophrenia That Can Be Modeled in Animals
Specific Animal Models
References
Part IX: Genetics
Chapter 31. Mouse Models for the Exploration of Klinefelter’s Syndrome
Acknowledgments
Introductory Remarks
KS—an Underestimated Disease
The X Chromosome in the Male
Clinical Features of KS
Sex Chromosomal Aberrations in Male Mammals
Mouse Models for KS
Lessons from Animal Experiments
Perspectives—What Can Be Expected from Future Animal Experiments and How to Retranslate Experimental Findings into Clinical Routine—Conclusive Remarks
References
Chapter 32. Genetically Tailored Pig Models for Translational Biomedical Research
Acknowledgments
Introduction
Techniques for the Production of Genetically Engineered Pigs
Genetically Engineered Pigs as Models for Human Diseases
Conclusions
References
Chapter 33. Genetically Modified Animal Models
Introduction
Some Historical Aspects
Techniques for the Managed Creation of Genetically Modified Animal Models
Types of Genetically Modified Animals and How They Are Produced
Genetically Modified Mice as Models of Human Diseases
References
Chapter 34. Mouse Models for Human Diseases by Forward and Reverse Genetics
Acknowledgments
Genetics and Diseases
Genetic or Environmental Factors
Power of Mouse Models for Human Diseases
The Human Genome Project and Human Diseases
Basic Genetics for Developing and Using Model Mice
Mutant Mice as Disease Models
Unique Positional Cloning: High Reversion Rates of dv and pun Mutations
Mutagenesis for Forward Genetics
Mutagenesis for Reverse Genetics
Concluding Remarks
References
Part X: Early Life
Chapter 35. Animal Models for the Study of Infection-Associated Preterm Birth
Acknowledgment
Introduction
Infection, Inflammation, and Parturition
Practical Study: Surgical Studies in the Pregnant Sheep
References
Chapter 36. Animal Models of Febrile Seizures
Acknowledgments
Introduction
Febrile Seizure in Humans and Its Relationship to Epilepsy
Animal Models of Febrile Seizures
Other Animal Models of Early-Life Seizures
Mechanisms Underlying Hyperthermia-Induced Experimental Febrile Seizures
Neuroanatomical Changes after Experimental Febrile Seizures
Neurophysiological Changes after Experimental Febrile Seizures
Neuronal Hyperactivity after Experimental Febrile Seizures
Behavioral Changes after Experimental Febrile Seizures
Conclusions
References
Part XI: Viral Disease
Chapter 37. Human Herpesviruses and Animal Models
Acknowledgments
Introduction
CMV (HHV-5) and Other Betaherpesviruses (HHV-6 and -7)
Gammaherpesviruses (Epstein–Barr Virus and Kaposi’s Sarcoma-Associated Herpesvirus)
Herpes Simplex (HSV-1 and -2)
Varicella Zoster (HHV-4)
Recombinant Viruses and Reporter Genes
Protocols
Protocol 1. Generation of Mutants via Conventional Homologous Strategy
Protocol 2. Generation of Recombinant Virus via Manipulation of an Infectious BAC Clone
Protocol 3. Virus Titration
Protocol 4. Detection and Tracking of Cells in Response to Virus Infection
Bioluminescent Tracking of Immune Cells during Viral Brain Infection
Protocol 5. Detection of Viral Load in Target Organs of Virus-Infected Animals (CMV, HSV, and VZV)
Protocol 6. BLI of Virus Infection in an Animal Model
References
Chapter 38. Animal Models of Human Viral Diseases
Introduction
Picornaviridae
Caliciviridae
Togaviridae
Flaviviridae
Coronoviridae
Rhabdoviridae
Filoviridae
Paramyxoviridae
Orthomyxoviridae
Bunyaviridae
Arenaviridae
Reoviridae
Retroviridae
Papillomaviridae
Poxviridae
Hepadnaviridae
Conclusions
References
Part XII: Cancer
Chapter 39. Xenograft, Transgenic, and Knockout Models of Prostate Cancer
Introduction
Xenograft Models of Prostate Cancer
The LOBUND–Wistar Rat Model of Prostate Cancer
Transgenic Models of Prostate Cancer
Knockout Models of Prostate Cancer
Transgenic Models of the Tumor Microenvironment
References
Chapter 40. Animal Models for Studying Prevention and Treatment of Breast Cancer
Introduction to Animal Models of Breast Cancer
Concepts of Breast Cancer Biology
Modeling Breast Cancer in Rodents
Spontaneous and Induced Mammary Tumorigenesis in Rodents
Grafting and Transplantation Approaches
Genetically Engineered Mice Models of Breast Cancer
References
Part XIII: Sclerosis
Chapter 41. Animal Models of Systemic Sclerosis
Introduction
Bleomycin-Induced Murine Scleroderma
HOCl-Induced Murine Scleroderma
Tsk Mouse
Scl-GvHD Model
Skin Fibrosis by Exogenous Injection of Growth Factors
UCD-200 Chicken
Transgenic Mouse Models
Knockout Mouse Models
Conclusions
References
Chapter 42. Animal Models for the Study of Multiple Sclerosis
The Complex Biology of Multiple Sclerosis
Immunological Models for CNS Demyelination
Local Induction of Demyelination following Injection of Myelin Peptides
Development of MS Therapies Based on Models of Immune-Mediated Demyelinating Diseases
Viral-Mediated Models of Demyelination
Oligodendrocyte-Induced Cell Death Models of Demyelination
Toxin Models of Demyelination
Conclusions and Comments
References
Index
Details
- No. of pages:
- 1108
- Language:
- English
- Copyright:
- © Academic Press 2013
- Published:
- 22nd July 2013
- Imprint:
- Academic Press
- Hardcover ISBN:
- 9780124158948
- eBook ISBN:
- 9780124159129
About the Editor
P. Michael Conn
P. Michael Conn is the Senior Vice President for Research and Associate Provost, Texas Tech Health Sciences Center. He is The Robert C. Kimbrough, Professor of Internal Medicine and Cell Biology/Biochemistry. He was previously Director of Research Advocacy and Professor of Physiology and Pharmacology, Cell Biology and Development and Obstetrics and Gynecology at Oregon Health and Science University and Senior Scientist of the Oregon National Primate Research Center (ONPRC). He served for twelve years as Special Assistant to the President and Associate Director of the ONPRC. After receiving a B.S. degree and teaching certification from the University of Michigan (1971), a M.S. from North Carolina State University (1973), and a Ph.D. degree from Baylor College of Medicine (1976), Conn did a fellowship at the NIH, then joined the faculty in the Department of Pharmacology, Duke University Medical Center where he was promoted to Associate Professor in 1982. In 1984, he became Professor and Head of Pharmacology at the University of Iowa College of Medicine, a position he held for eleven years. Conn is known for his research in the area of the cellular and molecular basis of action of gonadotropin releasing hormone action in the pituitary and therapeutic approaches that restore misfolded proteins to function. His work has led to drugs that have benefitted humans and animals. Most recently, he has identified a new class of drugs, pharmacoperones, which act by regulating the intracellular trafficking of receptors, enzymes and ion channels. He has authored or co-authored over 350 publications in this area and written or edited over 200 books, including texts in neurosciences, molecular biology and endocrinology. Conn has served as the editor of many professional journals and book series (Endocrinology, Journal of Clinical Endocrinology and Metabolism, Endocrine, Methods, Progress in Molecular Biology and Translational Science and Contemporary Endocrinology). Conn served on the National Board of Medical Examiners, including two years as chairman of the reproduction and endocrinology committee. The work of his laboratory has been recognized with a MERIT award from the NIH, the J.J. Abel Award of the American Society for Pharmacology and Experimental Therapeutics, the Weitzman, Oppenheimer and Ingbar Awards of the Endocrine Society, the National Science Medal of Mexico (the Miguel Aleman Prize) and the Stevenson Award of Canada. He is the recipient of the Oregon State Award for Discovery, the Media Award of the American College of Neuropsychopharmacology and was named a distinguished Alumnus of Baylor College of Medicine in 2012. Conn is a previous member of Council for the American Society for Cell Biology and the Endocrine Society and is a prior President of the Endocrine Society, during which time he founded the Hormone Foundation and worked with political leadership to heighten the public’s awareness of diabetes. Conn’s students and fellows have gone on to become leaders in industry and academia. He is an elected member of the Mexican Institute of Medicine and a fellow of the American Association for the Advancement of Science. He is the co-author of The Animal Research War (2008) and many articles for the public and academic community on the value of animal research and the dangers posed by animal extremism. His op/eds have appeared in The Washington Post, The LA Times, The Wall Street Journal, the Des Moines Register, and elsewhere. Conn consults with organizations that are influenced by animal extremism and with universities and companies facing challenges from these groups.
Affiliations and Expertise
Texas Tech University Health Sciences Center, Lubbock, USA
Reviews
"...addresses how to locate resources, animal alternatives, animal ethics and related issues, much needed information for researchers across the biological sciences and biomedicine."--Anticancer Research, February 2015
"…a very detailed textbook for researchers and laboratory animal veterinarians interested in getting an understanding of some of the animal models of human diseases. The authors have done a good job of reviewing the numerous animal models in various physiological systems."--Laboratory Animal Practitioner, June 2014
"…overall, the content (figures, tables and descriptions of the animal models and their significance) is excellent and should be considered a useful resource…Any laboratory animal research program, particularly those with an interest in working with multiple species of animal models, would benefit from having this book in the library."--Lab Animal, February 2014
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