Humanized Mouse Models To Study Immune Responses To Human Infectious Organisms

Topic Editor Prof. Aimin Xu receives financial support from Servier Laboratories. The other Topic Editors declare no competing interests with regards to the Research Topic theme.

Over the last several years the field of humanized mice has matured and developed into an essential component of translational research for HIV/AIDS. Humanized mice serve both as vehicles for discovery and as highly sophisticated platforms for biomedical research. In addition, humanized mice have demonstrated outstanding potential for the investigation of critical aspects of the infection and pathogenesis of the hepatitis and herpes viruses, as well as highly relevant microbial infections such as tuberculosis and malaria. Humanized Mice for HIV Research provides a comprehensive presentation of the history, evolution, applications, and current state of the art of this unique animal model. An expansion of twelve review articles that were published in Humanized Mice by Springer in 2008 (Eds: Nomura T, Watanabe T, Habu S), this book expertly captures the outstanding progress that has been made in the development, improvement, implementation, and validation of humanized mouse models. The first two parts of this book cover the basics of human-to-mouse xenotransplantation biology, and provide critical information about human immune cell development and function based on individual models created from different immunodeficient strains of mice. The third and fourth parts investigate HIV-1 biology, including different routes of transmission, prevention, treatment, pathogenesis, and the development of adaptive immunity in humanized mice. The fifth part shows the broad applicability of humanized mice for therapeutic development, from long-acting antiretroviral combinations to genetic manipulations with human cells and cell-based approaches. The sixth part includes liver tissue engineering and the expansion of humanized mice for many other human cell-tropic pathogens.

The innate immune system represents a critical arm of the immune response by providing immediate and robust host defense; however, human studies of its function are often limited by ethical, logistical, and technical obstacles. In Mouse Models of Innate Immunity: Methods and Protocols, experts in the field explore the design and execution of experiments used to thoroughly evaluate critical elements associated with the host innate immune response. The volume opens with methods that are essential for collecting and assessing various primary cells that are highly relevant to innate immunity, and it continues with in vivo protocols commonly used to evaluate the innate immune response in the mouse, including mouse models of respiratory infection, gastrointestinal inflammation, fungal and parasitic diseases, sepsis, and HIV-1 infection. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and easy to use, Mouse Models of Innate Immunity: Methods and Protocols will serve the research community by providing expert advice and protocols that allow both experienced and novice investigators to successfully plan, implement, and assess disease processes associated with the innate immune response.

The term humanized mouse in this text refers to a mouse in which human tissues and cells have been transplanted and show the same biological function as they do in the human body. That is, the physiological properties and functions of tra- planted human tissues and cells can be analyzed in the mouse instead of using a living human body. It should therefore be possible to study the pathophysiology and treatment of human diseases in mice with good reproducibility. Thus, the hum- ized mouse can be used as a potent tool in both basic and clinical research in the future. The development of appropriate immunodeficient mice has been indispensable in the creation of the humanized mouse, which has been achieved through many years of efforts by several laboratories. The first stage on the road to the humanized mouse was the report on nude mice by Isaacson and Cattanach in 1962. Thereafter, nude mice were studied in detail by Falanagan and, in 1968, Pantelouris found that these mice have no thymus gland, which suggested that the mice lack transplan- tion immunity against xenografts such as human hematopoietic stem cells. At the Nude Mouse Workshops (organized by Regard, Povlsen, Nomura and colleagues) that were held nine times between 1972 and 1997, the possibility of creating a humanized mouse using nude mice was extensively examined. The results, however, showed that certain human cancers can be engrafted in nude mice, but unfortunately engraftment of normal human tissue was almost impossible.

For many years, experiments using chimpanzees have been instrumental in advancing scientific knowledge and have led to new medicines to prevent life-threatening and debilitating diseases. However, recent advances in alternate research tools have rendered chimpanzees largely unnecessary as research subjects. The Institute of Medicine, in collaboration with the National Research Council, conducted an in-depth analysis of the scientific necessity for chimpanzees in NIH-funded biomedical and behavioral research. The committee concludes that while the chimpanzee has been a valuable animal model in the past, most current biomedical research use of chimpanzees is not necessary, though noted that it is impossible to predict whether research on emerging or new diseases may necessitate chimpanzees in the future.

This book comprehensively reviews the anatomy, physiology, genetics and pathology of laboratory animals as well as the principles and practices of using laboratory animals for biomedical research.It covers the design of buildings used for laboratory animals, quality control of laboratory animals, and toxicology, and discusses various animal models used for human diseases. It also highlights aspects, such as handling and restraint and administration of drugs, as well as breeding and feeding of laboratory animals, and provides guidelines for developing meaningful experiments using laboratory animals.Further, the book discusses various alternatives to animal experiments for drug and chemical testing, including their advantages over the current approaches. Lastly, it examines the potential effect of harmful pathogens on the physiology of laboratory animals and discusses the state of art in in vivo imaging techniques.The book is a useful resource for research scientists, laboratory animal veterinarians, and students of laboratory animal medicine.