Transgenic Neuroscience Research

To examine the promise, concerns, and challenges related to neuroscience research using genetically modified nonhuman primates, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop on October 4, 2018, bringing together an international group of experts and stakeholders representing academia, industry, laboratory animal management, disease-focused foundations, and federal agencies. The workshop was designed to explore the current state and future promise of research using genetically modified nonhuman primate models of disease to understand the complex functions of the brain that control behavior, movement, and cognition in both health and disease states. This publication summarizes the presentations and discussions from the workshop.

As the presence of genetically modified animal models in research laboratories has multiplied, the role of genetic factors in the pathogenesis of brain disorders has become particularly important. The refinement of molecular genetic methods has continued to broaden our understanding of the genetic factors associated with a variety of disorders. In "Transgenic and Mutant Tools to Model Brain Disorders", leading scientists specializing in this field contribute a timely collection of recent advances featuring a vast array of topics in order to contribute to the diverse approaches taken toward the evaluation of genetically modified models in biomedical research. Opening with several chapters covering general aspects of genetically modified animal models, the book then continues with detailed chapters on models of specific human brain disorders, including OCD, Rett Syndrome, anxiety disorders, depression, and schizophrenia. As a volume in the successful NeuromethodsTM series, the chapters provide authoritative reviews covering the most commonly used approaches in the field. Cutting-edge and concise, "Transgenic and Mutant Tools to Model Brain Disorders" offers a comprehensive and descriptive overview on a variety of topics in neuroscience and biological psychiatry.

In this up-to-date survey and critical assessment of transgenic and knockout models in neuropsychiatry and behavior, a panel of leading researchers comprehensively assesses how and whether the genetic abnormalities produced from these models manifest the neuropsychiatric disorders to which they correspond. The authors focus on transgenic and knockout models of neurocognitive dysfunction and neuropsychiatric dysfunction. The discussion of neurobiological problems covers mental retardation, polyglutamate, and speech disorders, as well as disorders that involve cognitive, social, speech, and language dysfunction. The neuropsychiatric dysfunctions examined include psychosis and schizophrenia, anxiety, depression, and bipolar disorder.

The marmoset, a type of small monkey native to South America, is a research model of increasing importance for biomedical research in the United States and globally. Marmosets offer a range of advantages as animal models in neuroscience, aging, infectious diseases, and other fields of study. They may be particularly useful for the development of new disease models using genetic engineering and assisted reproductive technologies. However, concerns have been voiced with respect to the development of new marmoset-based models of disease, ethical considerations for their use, the supply of marmosets available for research, and gaps in guidance for their care and management. To explore and address these concerns, the Roundtable on Science and Welfare in Laboratory Animal Use hosted a public workshop on October 22-23, 2018, in Washington, DC. The workshop focused on the availability of marmosets in the United States and abroad; animal welfare and ethical considerations stemming from the use of wildtype and genetically modified marmosets; and standards of housing and care, dietary needs, and feeding requirements for marmosets in captivity. This publication summarizes the presentations and discussions from the workshop.

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.

Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic

Animals are widely used in neuroscience research to explore biological mechanisms of nervous system function, to identify the genetic basis of disease states, and to provide models of human disorders and diseases for the development of new treatments. To ensure the humane care and use of animals, numerous laws, policies, and regulations are in place governing the use of animals in research, and certain animal regulations have implications specific to neuroscience research. To consider animal research regulations from a global perspective, the IOM Forum on Neuroscience and Nervous System Disorders, in collaboration with the National Research Council and the Institute for Laboratory Animal Research, held a workshop in Buckinghamshire, UK, July 26-27, 2011. The workshop brought together neuroscientists, legal scholars, administrators, and other key stakeholders to discuss current and emerging trends in animal regulations as they apply to the neurosciences. This document summarizes the workshop.

The need to better understand the molecular, b- chemical, and cellular processes by which a developing neuronal system unfolds has led to the development of a unique set of experimental tools and organisms. Special emphasis was devoted to allowing us access, at the ear- est stages, to the genomic basis underlying the system’s ultimate complexity, as exhibited once its structures are fully formed. Yet, nerve cells are anatomically, physiolo- cally, and biochemically diverse. The multitude of d- tinctly different routes for their development thus makes the developing nervous system especially intriguing for molecular neurobiologists. In particular, the demands of modern molecular neuroscience call for the establishment of efficient yet versatile systems for studying these c- plex processes. Transgenic embryos of the frog Xenopus laevis offer an excellent system for approaching neuroscientific issues. Insertion of foreign genes is performed simply, by mic- injection under binocular observation; hundreds of in vitro-fertilized embryos can be microinjected in one experiment. Embryos develop in tap water, at room t- perature, and within a few days become independent swimming tadpoles with fully functioning neuromus- lar systems. Being relatively small, these organisms are amenable to detailed analyses at the levels of mRNA, protein, and cell. Their rapid development permits the study of morphogenetic processes involved in early development, such as myogenesis and neural induction, as well as those involved in organogenesis and formation of the brain, the musculature, and the interconnections between them. Foreign DNA remains predominantly extrachromosomal.