Pathology of Genetically Engineered and Other Mutant Mice. Группа авторов

of Pathobiology & Laboratory Medicine University of Toronto Toronto, Canada

      Sébastien Monette, DMV, MVSc, Dipl. ACVP Laboratory of Comparative Pathology Memorial Sloan Kettering Cancer Center The Rockefeller University Weill Cornell Medicine New York, NY, USA

      Alexander Yu. Nikitin, MD, PhD Department of Biomedical Sciences NYS College of Veterinary MedicineCornell University Ithaca, NY, USA

      Michelle N. Perry, PhD Mouse Genome Informatics The Jackson Laboratory Bar Harbor, ME, USA

      Alessandra Piersigilli, DVM, PhD, Dipl. ECVP Drug Safety Research & Evaluation Takeda Pharmaceuticals International Co. Cambridge, MA, USA

      Enrico Radaelli, DVM, PhD, Dipl. ECVP Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia, PA, USA

Jerold E. Rehg, DVM, Dipl. ACVP, Dipl. ACLAM Pathology Department St. Jude Children’s Research Hospital Memphis, TN, USA

      Avi Z. Rosenberg, MD, PhD, Dipl. ABPath Division of Kidney‐Urologic Pathology Department of Pathology Johns Hopkins Medical Institutions Baltimore, MD, USA

      Sara F. Santagostino, DVM, PhD, Dipl. ACVP Department of Safety Assessment Genentech, Inc. South San Francisco, CA, USA

      Paul N. Schofield, PhD Department of Physiology, Development and Neuroscience University of Cambridge Cambridge, UK

      David Shaw, PhD The Jackson Laboratory Bar Harbor, ME, USA

      Heather W. Sheppard, DVM, PhD, Dipl. ACVP Pathology Department St. Jude Children's Research Hospital Memphis, TN, USA

      Jessica M. Snyder DVM, MS, Dipl. ACVIM and Dipl. ACVP Department of Comparative Medicine School of MedicineUniversity of Washington Seattle, WA, USA

      Katja Steiger, DVM, PD, Dr. Med. Vet. Habil., FTA Pathology Comparative Experimental Pathology Institute of Pathology, School of Medicine Technical University of Munich (TUM) Munich, Germany

      John P. Sundberg, DVM, PhD, Dipl. ACVP The Jackson Laboratory Bar Harbor, ME, USA and Department of Dermatology Vanderbilt University Medical Center Nashville TN, USA and North Woods Mouse Pathology Southwest Harbor, ME, USA

      Polina Sysa‐Shah, MD Department of Urology School of Medicine Johns Hopkins University Baltimore, MD, USA

      Piper M. Treuting, DVM, MS, Dipl. ACVP Non‐clinical Sciences Seattle Genetics Bothell, WA, USA

      Peter Vogel, DVM, PhD, Dipl. ACVP Pathology Department St. Jude Children's Research Hospital Memphis, TN, USA

      Jerrold M. Ward, DVM, PhD, Dipl. ACVP, Fellow IATP Global VetPathology Montgomery Village, MD, USA

      M. Kay Washington, MD, PhD, Dipl. ABPath Department of Pathology, Microbiology and Immunology Vanderbilt University Medical Center Nashville, TN, USA

      Preface and Acknowledgments

      The editors of this book want to take this opportunity to acknowledge and thank our wives for supporting us through this process. Beth Sundberg, Jane Vogel, and Ann Ward supported us as we wrote our respective and coauthored chapters, and as we reviewed all the submissions from the numerous experts who carefully drafted the chapters that follow. This was a large undertaking by all involved, and we believe that this book will serve as a resource for many years to come to assist scientists in the development and interpretation of mouse models for the study of human diseases.

      The pathologists and other scientists who wrote these chapters while examining the mice, overseeing necropsies, and evaluating the histologic sections of tissues of interest, need to take this opportunity to thank the laboratory animal staff including veterinarians and animal care technicians who managed these mouse colonies, the necropsy/laboratory technicians who performed the postmortem examinations and collected tissues for a variety of histological and molecular assays, as well as the histologists who processed the tissues, prepared sections, and stained them with a variety of histochemical stains and immunological markers. The end result of these largely anonymous contributions have been the excellent histologic sections all authors photographed. We also would like to thank all of our collaborators over the years who allowed us to participate with them on the many experiments using mice for studying the causes and mechanisms of both human and animal disease, and the search for effective disease therapies and methods of prevention experiments. In addition, the Wiley publication staff was invaluable for creation of this book. We greatly appreciate their help.

      The purpose of this book is to provide a broad overview on how pathologists phenotype mutant and wild‐type (without an induced or natural gene mutation) mice and compare them to human diseases. Each chapter covers one organ or organ system with a brief overview of the anatomy, but more importantly, specifics on tissue collection, processing, and special stains or assays used to analyze that particular organ. Each chapter is written by one or more experts on that organ. In so doing, this book provides a useful starting point for investigators working with mice, be they experts or neophytes.

      Nomenclature is a critical aspect of pathological description. Pathologists learn to critically utilize very specific medical terms to describe gross and histologic features of lesions and that is evident throughout this book. However, equally important when working with mice, humans, rats, and many other laboratory species, is the species‐specific nomenclature for genes and proteins. Reviews, especially books, should compile information on specific topics to provide an up‐to‐date overview, including using current molecular nomenclature. While this is required by most journals, few editors or reviewers pay much attention to nomenclature accuracy. Because we felt this was such an important and largely overlooked topic, there is a detailed chapter on this subject in this book. The editors made a decided effort to review all chapters not only for accuracy of the pathological descriptions and terms but also for molecular nomenclature. Ultimately, the chapter authors were free to decide whether or not to use the current terms, including listing the specific allelic mutations they were discussing, and most did. We want to specifically thank Michelle Perry, David Shaw, and Dale Begley from the Mouse Genome Informatics Database group at the Jackson Laboratory for following up on all of our inquiries to make sure we did our best to get the nomenclature correct. This included in a number of cases getting new names assigned to mouse mutant alleles that were recently published.

The real value for updating genetic nomenclature became obvious in many of the chapters as they were being reviewed. Defining an animal model of a human disease depends on closely matching the disease features (phenotypes) between the animal under investigation (the mouse) and humans in particular. Over the years, lab names were given to the animals, often indicating something about their phenotype(s). These names became embedded within “the field” to the point they were considered to be standard names. The mouse genetic community many years ago set up the International Committee on Standardized Genetic Nomenclature for Mice (http://www.informatics.jax.org/mgihome/nomen/inc.shtml). This is housed at the Jackson Laboratory within the Mouse Genome Informatics Database (MGI), but the committee consists of geneticists from around the world. They have sought to regularly review and adjust genetic nomenclature as new information is published on genes, biological pathways, and gene functions. In so doing, names change over the years. MGI maintains this information, which includes reported allelic mutations and links to many of the publications about that mutant mouse line. The surprise that came up consistently in all chapters was that as the mutant gene became known, and the names updated, it was obvious that not only did the mouse model often closely resemble the human disease, but since human genetic nomenclature had followed a similar course with updates in names, in most cases the orthologous gene was mutated in both species, an important point in validating the disease model.