Pathology of Genetically Engineered and Other Mutant Mice

Melissa L. Berry, MS, MBAThe Jackson Laboratory Bar Harbor, ME, USA

Brad Bolon, DVM, MS, PhD, Dipl. ACVP, Dipl. ABT, Fellow ATS, Fellow IATP, Fellow RCPathGEMpath Inc. Longmont, CO, USA

Alexander D. Borowsky, MD, Dipl. ABPathDepartment of Pathology and Laboratory Medicine Center for Immunology and Infectious Diseases Center for Genomic Pathology University of California, Davis Davis, CA, USA

Cory F. Brayton, DVM, Dipl. ACVP, Dipl. ACLAMDepartment of Molecular and Comparative Pathology School of Medicine Johns Hopkins University Baltimore, MD, USA

Robert D. Cardiff, MD, PhD, Dipl. ABPathDepartment of Pathology and Laboratory Medicine Center for Immunology and Infectious Diseases Center for Genomic Pathology University of California, Davis Davis, CA, USA

Lucas M. Chaible, PhDLaboratory of Experimental and Comparative Oncology School of Veterinary Medicine and Animal Science University of Sao Paulo Sao Paulo, SP, Brazil

Timothy K. Cooper, DVM, PhD, Dipl. ACVPLaulima Government Solutions – Contractor Supporting National Institute of Allergy and Infectious Diseases, NIH Integrated Research Facility Division of Clinical Research Frederick, MD, USA

Tyler J. Creamer, PhDDepartments of Surgery and Genetic Medicine School of Medicine Johns Hopkins University Baltimore, MD, USA

Maria L.Z. Dagli, DVM, MSc, PhD, Fellow IATPLaboratory of Experimental and Comparative Oncology Department of Pathology School of Veterinary Medicine and Animal Science University of Sao Paulo Sao Paulo, SP, Brazil

Darlene Dixon, DVM, PhD, Dipl. ACVP, Fellow, IATPMolecular Pathogenesis Group NTP Laboratory NIEHS Research Triangle Park, NC, USA

Jeffrey I. Everitt, DVM, Dipl. ACVP, Dipl. ACLAMDepartment of Pathology Duke University School of MedicineDurham, NC, USA

Kathleen L. Gabrielson, DVM, PhD, Dipl. ACVPDepartments of Molecular and Comparative Pathology Pathology and Oncology and Environmental Health Engineering School of Medicine and Bloomberg School of Public Health Johns Hopkins University Baltimore, MD, USA

Katherine N. Gibson‐Corley, DVM, PhD, Dipl. ACVPDepartment of Pathology, Microbiology and Immunology Vanderbilt University Medical Center Nashville, TN, USA

Virginia L. Godfrey, DVM, PhD, Dipl. ACVPDivision of Comparative Medicine Department of Pathology and Laboratory Medicine School of MedicineUniversity of North Carolina Chapel Hill, NC, USA

Harm HogenEsch, DVM, PhD, Dipl. ACVPDepartment of Comparative Pathobiology College of Veterinary Medicine Purdue UniversityWest Lafayette, IN, USA

Laura J. Janke, DVM, PhD, Dipl. ACVPPathology Department St. Jude Children's Research Hospital Memphis, TN, USA

Lloyd E. King, Jr., MD, PhD, Dipl. DPDepartment of Dermatology Vanderbilt University Medical Center Nashville, TN, USA

Sue E. Knoblaugh, DVM, Dipl. ACVPComparative Pathology & Digital Imaging Shared Resource Department of Veterinary Biosciences College of Veterinary Medicine The Ohio State University Columbus, OH, USA

Jeffrey B. Kopp, MD, Dipl. ABIM (Nephrology)Kidney Diseases Branch NIDDK National Institutes of Health Bethesda, MD, USA

Raoul V. Kuiper, PhD, DVM, Dipl. ECVPDepartment of Laboratory Medicine Karolinska University Hospital Huddinge Stockholm, Sweden

Krista M. D. La Perle, DVM, PhD, Dipl. ACVPComparative Pathology & Digital Imaging Shared Resource Department of Veterinary BiosciencesCollege of Veterinary Medicine Columbus, OH, USA

Colin McKerlie, DVM, DVSc, MRCVSTranslational Medicine Research Program The Hospital for Sick Children Toronto, Canada and Faculty of Medicine Department of Pathobiology & Laboratory Medicine University of Toronto Toronto, Canada

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

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

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

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

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

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

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

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

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

David Shaw, PhDThe Jackson Laboratory Bar Harbor, ME, USA

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

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

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

John P. Sundberg, DVM, PhD, Dipl. ACVPThe 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, MDDepartment of Urology School of Medicine Johns Hopkins University Baltimore, MD, USA

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

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

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

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

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.