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What's Wrong With My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice, 2nd Edition



What's Wrong With My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice, 2nd Edition

Jacqueline N. Crawley

ISBN: 978-0-470-11904-4 May 2007 544 Pages

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Dr. Jacqueline N. Crawley, author of the First and Second Editions of What’s Wrong with My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice,continues to field calls and e-mails from molecular geneticists who ask: how do I run behavioral assays to find out what’s wrong with my mouse?

Turn to What’s Wrong with My Mouse? to discover the wealth of mouse behavioral tasks and to get the guidance you need to select the best methods and necessary controls. Chapters are organized by behavioral domain, including measurements of general health, motor functions, sensory abilities, learning and memory, feeding and drinking, reproductive, social, emotional, and reward behaviors in mutant mice. Throughout the chapters, new behavioral tasks and new research discoveries have been added, bringing the Second Edition up to date with the latest science. In addition, the Second Edition includes two new chapters:

"Neurodevelopment and Neurodegeneration" discusses mouse behavioral tasks relevant to neurodevelopmental diseases, such as mental retardation and autism, and to neurodegenerative diseases, such as Alzheimers, Parkinsons, Huntingtons, and amyotrophic lateral sclerosis.

"Putting It All Together" recommends strategies for optimizing a battery of behavioral phenotyping tests to address your specific hypotheses about gene functions.

The final chapter, "The Next Generation," examines new and emerging technologies.

Throughout the book, the use of behavioral testing equipment is illustrated with photographs, diagrams, and representative data. Examples of behavioral tasks successfully applied to transgenic and knockout mouse models are provided, as well as references to the primary literature and step-by-step methods protocols. These features, along with a comprehensive index, listings of database and vendor websites, and an extensive list of references, make this book a valuable and practical resource for students and researchers.

Preface ix

Preface to the First Edition xi

Acknowledgments xiii

Chapter 1 Designer Mice 1

Scope and sourcebooks

Chapter 2 Of Unicorns and Chimeras 10

How to generate a line of transgenic or knockout mouse for behavioral phenotyping

Chapter 3 General Health 42

Give your mouse a physical

Chapter 4 Motor Functions 62

Open field, holeboard, rotarod, balance, grip, circadian activity, circling, stereotypy, ataxic gait, seizures

Chapter 5 Sensory Abilities 86

Olfaction, vision, hearing, taste, touch, nociception

Chapter 6 Learning and Memory 110

Morris swim task, spatial mazes, cued and contextual conditioning, conditioned taste aversion, conditioned eyeblink, olfactory discrimination, social recognition, passive avoidance, schedule controlled operant tasks, motor learning, attention

Chapter 7 Feeding and Drinking 164

Daily consumption, restricted access, choice tests, microstructural analysis

Chapter 8 Reproductive Behaviors 186

Sexual and parental behaviors

Chapter 9 Social Behaviors 206

Social interaction, nesting, grooming, juvenile play, aggression

Chapter 10 Emotional Behaviors: Animal Models of Psychiatric Diseases 226

Mouse models of fear, anxiety, depression, schizophrenia

Chapter 11 Reward 266

Self-administration of addictive drugs, conditioned place preference

Chapter 12 Neurodevelopment and Neurodegeneration 290

Assaying behaviors in infant, juvenile, and aged mice

Chapter 13 Putting It All Together 322

Choice of tests, order of testing, number of mice, equipment, housing and testing environment

Chapter 14 The Next Generation 344

Conditional and inducible mutations, viral vector gene delivery, RNA silencing, quantitative trait loci analysis, DNA microarrays, chemical mutagenesis, gene therapy, ethical issues

References 383

Index 503

This edition has been expanded to provide coverage of developmental and neurodegenerative diseases. In addition, it provides a new practical chapter with expert recommendations on determining which tasks to use for evaluation of a new line of mutant mice. The author discusses choice of genetic background, tests, sequence of testing, timing of sequence, and data interpretation for both comprehensive phenotyping and rapid, high-throughput screening.
First Edition Reviews:

"The book successfully brings together the field of behavioral neuroscience and the rewards and insights that can be gained using this approach. I would recommend that every behavioral scientist has at least two copies, one for their own use and one that will be on permanent load to their students, post-doctoral students and colleagues in molecular biology." (Trends in Pharmaceutical Sciences)

"the overall impression is of a helpful guide taking the reader step by step through the complexities of animal behavioral research." (Nature Neuroscience)

"succeeds as a useful introduction to the realm of behavioral phenotyping for those interested in creating or using the large and increasing number of promising targeted mutant mice." (Trends in Neurosciences)

  • Answers the questions: What are the best tests? What controls should be used? How do you avoid potential hidden pitfalls, false positives and negatives, and lurking artifacts? Which statistical tests can be applied?
  • Includes a new chapter on Developmental and Neurodegenerative Diseases, covering mental retardation and inborn errors of metabolism through to Alzheimer's disease and stroke
  • Provides brand new coverage of practical recommendations for choosing tasks to evaluate a new mutant line (Putting It All Together), including complete guidelines for high-throughput screening
  • Discusses implications of the completion of the mouse genome sequence, microarray technology, new gene delivery methods, stem cell transplantation, proteomics, and high throughput approaches in chemical mutagenesis studies
  • Expands discussion to the latest studies in learning and memory, autism and social phobias, olfaction, drug addiction, withdrawal, and spinal cord injury
  • Includes numerous new figures showing new behavioral tests, equipment, and data
  • Each chapter concludes with extensive, up-to-date references and suggestions for background reading