The dramatic recent expansion in genomic information has motivated the development of new approaches to characterize gene expression and function. A critical issue for both basic and clinical endocrinologists is the physiological role of genes involved in regulating endocrine functions. Transgenic technologies allow the translation of genotypic information into specific phenotypes by using gene overexpression or loss of specific gene functions. Murine functional genomics is thus of central importance in modem biomedical endocrine research. Although mice are at present, the preferred mammalian species for genetic manipulations because of the availability of pluripotent embryonic. stem cells and inbred strains and the relatively low breeding and maintenance costs, transgenic rats have also been generated and used to study endocrine physiology. The two basic techniques used in the creation of transgenic animal models are integration of foreign DNA into a fertilized oocyte by random chromosomal insertion and homologous recombination in embryonic stem cells that are then introduced into zygotes. Transgenic mice and rats serve as sophisticted tools to probe protein function, as models of human disease, and as hosts for the testing of gene replacement and other therapies. Embryonic stem cell libraries for mouse gene deletion are being developed, which will make it possible to generate knockout mice rapidly and without the need to analyze gene structure, construct targeting vectors, and screen embryonic stem cell clones. A novel approach to transgenesis for the expression of DNA within adult differentiated neuroendocrine cells in vivo is using viral vectors.

This timely volume provides a comprehensive overview of glucocorticoids and their role in regulating many aspects of physiology and their use in the treatment of disease. The book is broken into four sections that begin by giving a general introduction to glucocorticoids and a brief history of the field. The second section will discuss the effects of glucocorticoids on metabolism, while the third section will cover the effects of glucocorticoids on key tissues. The final section will discuss general topics, such as animal models in glucocorticoid research and clinical implications of glucocorticoid research. Featuring chapters from leaders in the field, this volume will be of interest to both researchers and clinicians.

Osteoporosis is one of the most clinically relevant disabling chronic disease encountered in clinical practice. A common cause of osteoporosis is glucocorticoid excess, as glucocorticoids may increase bone resorption, inhibit bone formation, have indirect actions on bone by decreasing intestinal calcium absorption and induce hypercalciuria. This book presents a comprehensive overview of the effects of glucocorticoids on bone metabolism and structure and on the diagnosis and treatment of glucocorticoid-induced osteoporosis. It aims at providing updated information on the pathogenesis, diagnosis and treatment of this often dramatic complication of glucocorticoid excess. Being one of the few publications completely devoted to glucocorticoid-induced osteoporosis it will heighten the awareness of specialists who prescribe glucocorticoids of the clinical relevance of this treatment complication. 'Glucocorticoid-Induced Osteoporosis' is addressed to clinical experts as well as to general practitioners who will both benefit from the comprehensive and integrative view of the management of patients exposed to glucocorticoids.

Expanding on the National Research Council's Guide for the Care and Use of Laboratory Animals, this book deals specifically with mammals in neuroscience and behavioral research laboratories. It offers flexible guidelines for the care of these animals, and guidance on adapting these guidelines to various situations without hindering the research process. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research offers a more in-depth treatment of concerns specific to these disciplines than any previous guide on animal care and use. It treats on such important subjects as: The important role that the researcher and veterinarian play in developing animal protocols. Methods for assessing and ensuring an animal's well-being. General animal-care elements as they apply to neuroscience and behavioral research, and common animal welfare challenges this research can pose. The use of professional judgment and careful interpretation of regulations and guidelines to develop performance standards ensuring animal well-being and high-quality research. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research treats the development and evaluation of animal-use protocols as a decision-making process, not just a decision. To this end, it presents the most current, in-depth information about the best practices for animal care and use, as they pertain to the intricacies of neuroscience and behavioral research.

Provides background information and detailed protocols for developing a mouse colony and using the animals in transgenic and gene-targeting experiments. The protocols list the animals, equipment, and reagents required and step-by-step procedures. Topics include in vitro culture of preimplantation embryos, surgical procedures, the production of chimeras, and the analysis of genome alterations. The third edition adds protocols for cloning mice, modifying embryonic stem cells, intracytoplasmic sperm injection, and cryopreservation of embryos.

The molecular genetics of aging or life-span determination is an expanding field. One reason is because many people would consider it desirable if hu man life span could be extended. Indeed, it is difficult not to be fascinated by tales of the life and death of people who have succeeded in living a very long life. Because of this, we have placed at the head of this book the chapter by Perls et al. on Centenerians and the Genetics of Longevity. Perls and his coauthors convincingly argue that, while the average life expectancy might be mostly determined by environmental factors because the average person has an average genotype, extremely long life spans are genetically determined. Of course, studying humans to uncover the genetics of aging is not ideal, not so much because one cannot easily perform experiments as because they live such a long time. This is why most of this book describes the current state of research with model organisms such as yeast, worms, flies, and mice. J aswinski focuses on yeast and how metabolic activity and stress resistance affect the longevity of Saccharomyces cerevisiae. In the process, he discusses the concept of aging as applied to a unicellular organism such as yeast and the importance of metabolism and stress resistance for aging in all organisms.

The application of recombinant DNA techniques to endocrinology is an exciting area of biomedical research. These and other new methods have made it possible to clone many endocrine genes--such as those for insulin and growth hormone--to determine their nucleatide sequences, and to study their expression both in vitro and in vivo. Derived from a series of molecular endocrinology research seminars, this book covers the basics of gene cloning, structural analysis and the regulation of gene expression in selected endocrine systems. The first part focuses on analytical methods and experimental approaches, including DNA-mediated gene transfer, identification of tissue-specific transcription factors and regulatory sequences, in situ hybridization of mRNA, and gene mapping on human chromosomes. The second part presents molecular studies of various endocrine systems, each combining different approaches.