The Reeler mutation was so named because of the alterations in gait that characterize homozygous mice. Several decades after the description of the Reeler phenotype, the mutated protein was discovered and named Reelin (Reln). Reln controls a number of fundamental steps in embryonic and postnatal brain development. A prominent embryonic function is the control of radial neuronal migration. As a consequence, homozygous Reeler mutants show disrupted cell layering in cortical brain structures. Reln also promotes postnatal neuronal maturation. Heterozygous mutants exhibit defects in dendrite extension and synapse formation, correlating with behavioral and cognitive deficits that are detectable at adult ages. The Reln-encoding gene is highly conserved between mice and humans. In humans, homozygous RELN mutations cause lissencephaly with cerebellar hypoplasia, a severe neuronal migration disorder that is reminiscent of the Reeler phenotype. In addition, RELN deficiency or dysfunction is also correlated with psychiatric and cognitive disorders, such as schizophrenia, bipolar disorder and autism, as well as some forms of epilepsy and Alzheimer's disease. Despite the wealth of anatomical studies of the Reeler mouse brain, and the molecular dissection of Reln signaling mechanisms, the consequences of Reln deficiency on the development and function of the human brain are not yet completely understood. This Research Topic include reviews that summarize our current knowledge of the molecular aspects of Reln function, original articles that advance our understanding of its expression and function in different brain regions, and reviews that critically assess the potential role of Reln in human psychiatric and cognitive disorders.

The Reeler mutation was so named because of the alterations in gait that characterize homozygous mice. Several decades after the description of the Reeler phenotype, the mutated protein was discovered and named Reelin (Reln). Reln controls a number of fundamental steps in embryonic and postnatal brain development. A prominent embryonic function is the control of radial neuronal migration. As a consequence, homozygous Reeler mutants show disrupted cell layering in cortical brain structures. Reln also promotes postnatal neuronal maturation. Heterozygous mutants exhibit defects in dendrite extension and synapse formation, correlating with behavioral and cognitive deficits that are detectable at adult ages. The Reln-encoding gene is highly conserved between mice and humans. In humans, homozygous RELN mutations cause lissencephaly with cerebellar hypoplasia, a severe neuronal migration disorder that is reminiscent of the Reeler phenotype. In addition, RELN deficiency or dysfunction is also correlated with psychiatric and cognitive disorders, such as schizophrenia, bipolar disorder and autism, as well as some forms of epilepsy and Alzheimer's disease. Despite the wealth of anatomical studies of the Reeler mouse brain, and the molecular dissection of Reln signaling mechanisms, the consequences of Reln deficiency on the development and function of the human brain are not yet completely understood. This Research Topic include reviews that summarize our current knowledge of the molecular aspects of Reln function, original articles that advance our understanding of its expression and function in different brain regions, and reviews that critically assess the potential role of Reln in human psychiatric and cognitive disorders.

The number of mouse models that are available for the study of human genetic neurological disorders is large and growing rapidly. Therefore, it was difficult to select the models that were reviewed in this volume. Clearly, there are important models that are not discussed, and perhaps a volume twice this size would have been more appropriate. Moreover, the pace at which new models are being developed and analyzed is rapid. As this volume goes to press, I am sure that additional mouse genes responsible for naturally occurring neurological disorders are being discovered and that many new transgenic and mutant mouse strains are being developed. Therefore, this volume should not be viewed as a comprehensive compendium, but rather as an update of work in progress. It is exhilarating to witness the fast pace at which these models are being established as important tools in the study of basic neuroscience and neurological disorders. It will be even more exciting to see their utilization in the development and testing of therapeutic interventions for these diseases. I would like to thank each of the authors who have contributed to this volume for their time and their expertise. I would also like to thank Drs. Timothy Coetzee and Joshua Corbin for their advice in the selection of the topics covered. I am deeply indebted to Dr. Kunihiko Suzuki, who first approached me with the idea for this volume, for his guidance throughout its preparation.

Nervous system diseases and disorders are highly prevalent and substantially contribute to the overall disease burden. Despite significant information provided by the use of animal models in the understanding of the biology of nervous system disorders and the development of therapeutics; limitations have also been identified. Treatment options that are high in efficacy and low in side effects are still lacking for many diseases and, in some cases are nonexistent. A particular problem in drug development is the high rate of attrition in Phase II and III clinical trials. Why do many therapeutics show promise in preclinical animal models but then fail to elicit predicted effects when tested in humans? On March 28 and 29, 2012, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders convened the workshop "Improving Translation of Animal Models for Nervous System Disorders" to discuss potential opportunities for maximizing the translation of new therapies from animal models to clinical practice. The primary focus of the workshop was to examine mechanisms for increasing the efficiency of translational neuroscience research through discussions about how and when to use animal models most effectively and then best approaches for the interpretation of the data collected. Specifically, the workshop objectives were to: discuss key issues that contribute to poor translation of animal models in nervous system disorders, examine case studies that highlight successes and failures in the development and application of animal models, consider strategies to increase the scientific rigor of preclinical efficacy testing, explore the benefits and challenges to developing standardized animal and behavioral models. Improving the Utility and Translation of Animal Models for Nervous System Disorders: Workshop Summary also identifies methods to facilitate development of corresponding animal and clinical endpoints, indentifies methods that would maximize bidirectional translation between basic and clinical research and determines the next steps that will be critical for improvement of the development and testing of animal models of disorders of the nervous system.

In recent years, medical developments have resulted in an increase in human life expectancy. Some developed countries now have a larger population of individuals aged over 64 than those under 14. One consequence of the ageing population is a higher incidence of certain neurodegenerative disorders. In order to prevent these, we need to learn more about them. This book provides up-to-date information on the use of transgenic mouse models in the study of neurodegenerative disorders such as Alzheimer's and Huntington's disease. By reproducing some of the pathological aspects of the diseases, these studies could reveal the mechanism for their onset or development. Some of the transgenic mice can also be used as targets for testing new compounds with the potential to prevent or combat these disorders. The editors have extensive knowledge and experience in this field and the book is aimed at undergraduates, postgraduates and academics. The chapters cover disorders including: Alzheimer's disease, Parkinson's disease, Huntington's and other CAG diseases, amyotrophic lateral sclerosis (ALS), recessive ataxias, disease caused by prions, and ischemia.

to the Animal Models Volumes This and several other volumes in the Neuromethods series will describe a number of animal models of neuropsychiatric disorders. Because of increasing public concern over the ethical treatment of animals in research, we felt it incumbent upon us to include this general preface to these volumes in order to indicate why we think further - search using animals is necessary and why animal models of psychiatric disorders, in particular, are so important. We recognize that animals should only be used when suitable alternatives are not available. We think it self-e- dent, however, that humans can only be experimented upon in severely proscribed circumstances and alternative pro- dures using cell or tissue culture are inadequate in any models requiring assessments of behavioral change or of complex in vivo processes. However, when the distress, discomfort, or pain to the animals outweighs the anticipated gains for human welfare, then the research is not ethical and should not be carried out. It is imperative that each individual researcher examine his/her own research from a critical moral standpoint - fore engaging in it, taking into consideration the animals’ welfare as well as the anticipated gains. Furthermore, once a decision to proceed with research is made, it is the researcher’s responsibility to ensure that the animals’ w- fare is of prime concern in terms of appropriate housing, feeding, and maximum reduction of any uncomfortable or distressing effects of the experimental conditions, and that these conditions undergo frequent formalized monitoring.

Reelin glycoprotein is a serine protease with important roles in embryogenesis and during adult life. This comprehensive and integrative book examines the role that reelin plays in the etiology of various neuropsychiatric disorders, including schizophrenia and autism. The book provides an unprecedented analysis of this emerging and novel protein by examining evidence from genetic, neuroanatomic, biochemical, and behavioral studies.