Pathology of Genetically Engineered and Other Mutant Mice

John P. Sundberg, Peter Vogel, Jerrold M. Ward, John P. Sundberg, Peter Vogel, Jerrold M. Ward

• Publisher: Wiley-Blackwell
• Year: 2021
• Print ISBN:
  9781119624578
• eBook ISBN:
  9781119624592
• Edition: 1
• Topic: Medicine
• Subtopic: Veterinary Medicine

An updated and comprehensive reference to pathology in every organ system in genetically modified mice

The newly revised and thoroughly updated Second Edition of Pathology of Genetically Engineered and Other Mutant Mice delivers a comprehensive resource for pathologists and biomedical scientists tasked with identifying and understanding pathologic changes in genetically modified mice. The book is organized by body system, includes descriptions and explanations of a wide range of findings, as well as hundreds of color photographs illustrating both common and rare lesions that may be found in genetically engineered and wild type mice.

The book is written by experienced veterinary and medical pathologists working in veterinary medical colleges, medical colleges, and research institutes. Covering the latest discoveries in mouse pathology resulting from advancements in biotechnology research over the last 30 years, this singular and accessible resource is a must-read for veterinary and medical pathologists and researchers working with genetically engineered and other mice.

Readers will also benefit from:

• A thorough introduction to mouse pathology and mouse genetic nomenclature, as well as databases useful for analysis of mutant mice
• An exploration of concepts related to validating animal models, including the Cinderella Effect
• Practical discussions of basic necropsy methods and grading lesions for computational analyses
• Concise diagnostic approaches to the respiratory tract, the oral cavity and GI tract, the cardiovascular system, the liver and pancreas, the skeletal system, and other tissues

As a one-stop and up to date reference on mouse pathology, Pathology of Genetically Engineered and Other Mutant Mice is an essential book for veterinary and medical pathologists, as well as for scientists, researchers, and toxicologists whose work brings them into contact with genetically modified mice.

1
Introduction to Mouse Pathology

Jerrold M. Ward, Peter Vogel, and John P. Sundberg

The Use of Mice in Medical Research

There has been a large increase in the use of mice in both basic and translational medical research over the past 20 years, as evidenced by the increase in retrievable references using “mice” as a keyword in PubMed from 29 029 publications in 1998 to 79 858 in 2018, and over 1.6 million in the entire PubMed database. Mice have been used for both basic and translational (formerly applied) research. Much of this important work is sponsored by the National Institutes of Health (NIH) in the United States. Mice have been used to study basic biological processes, embryo development, genetic disorders, infectious diseases, degenerative diseases, toxicology, carcinogenesis, and aging, often by organ system or tissue. Many Nobel Prize awardees in Physiology or Medicine have used mice in research leading to their honors. Much of this research has been greatly valued for the training of future scientists, discovery of new diseases, understanding the mechanism of disease in mice and other animals, including humans, and in the treatment and prevention of disease in mice and humans [1–8]. Histopathology may be included in the mouse research, but often it is not, or not by someone trained and competent in pathology [9]. The value of pathology has been proven for diagnosis and understanding normal biology and abnormal biology (pathology) of cells, tissues, and organs in all species. Comparative pathology spans all species of animals. But some investigators do not understand the value of pathology, as a discipline, in experimental studies with mice. This book intends to promote the value of mouse pathology in medical research aimed at the discovery of the causes, prevention, and therapy of diseases in both humans and other animals.

Understanding Diseases Found in Mutant Animals

Naturally occurring and induced changes in genes often result in a specific phenotype at the clinical and histopathological levels. The cause of this phenomenon is that genes have specific functions that play a role in the normal homeostasis of cells, tissues, and organs. A genetically engineered mouse () line represents a tool to investigate the effects resulting from the partial or complete loss of gene function or the gain of normal or abnormal functions. The genes are often found to function in specific cellular organelles and biochemical/molecular pathways important for normal biological functions (Figure 1.1) [10]. Cells involved in common gene functions can be single cell types in single tissues, multiple cells types in a single tissue, or multiple cells types in multiple tissues. Gene expression can also be induced in specific cells and tissues by normal and abnormal body functions, or by exposure to external factors such as drugs, infectious agents, environmental modifications, and ingested foods.

Mutant mice often exhibit histopathological changes (lesions) in tissues and organs that are associated with gene function, but the ultimate clinical phenotype can be influenced by various factors. Much of the histopathology found in mutant mice is in the usual spectrum of degenerative, inflammatory, proliferative, and neoplastic changes also found in nonmutant mice. Nouvelle lesions do occur commonly in some lines of mutant mice. These include unique developmental changes, cellular morphological changes, patterns of lesions, types of proliferative lesions, and often strain specific cancer types. These may be due to specific naturally occurring mutations (polymorphisms) in genes that can serve as genetic based models for disease. Spontaneous mutants made up the bulk of mouse models until the advent first of radiation and then chemical mutagenesis programs. The spectrum of spontaneous lesions is noted in each organ‐specific chapter. Often the lesions are identical or very similar to those associated human genetic disorders, but they also may vary from human lesions. The genetic background of the mice often plays a role in spontaneous as well as induced disease phenotypes.

Figure 1.1 Classes of proteins associated with human genetic diseases.

Source: Nussbaum (2007). Reprinted with permission of Elsevier

Mouse Pathology – Nomenclature

The pathology of mice in research was first led by Thelma Dunn and Harold Stewart at the National Cancer Institute (NCI) at the NIH [11–13]. Both were MD pathologists who applied general rules of human pathology diagnosis to mice when possible. Although mouse pathology nomenclature does not follow any official designation, two organizations (INHAND; https://www.toxpath.org/inhand.asp and National Cancer Institute Mouse Models of Cancer Consortium Tumor Pathology Nomenclature) have provided international nomenclatures for specific tissues [2, 14]. Other publis...

Table of contents

• Cover
• Table of Contents
• Title Page
• Copyright Page
• List of Contributors
• Preface and Acknowledgments
• 1 Introduction to Mouse Pathology
• 2 The Mouse Online: Open Mouse Biology and Pathology Data Resources for Biomedical Research
• 3 Mouse Genetic Nomenclature
• 4 Discovering and Validating Mouse Models of Human Diseases: The Cinderella Effect
• 5 Embryos, Placentas, and Neonates
• 6 Ciliopathies
• 7 Hematopoietic and Lymphoid Tissues
• 8 Mouse Hematolymphoid Neoplasms
• 9 Immunodeficient and Humanized Mice
• 10 Skin, Hair, and Nails
• 11 Mammary Gland
• 12 The Respiratory Tract
• 13 The Gastrointestinal Tract
• 14 Cardiovascular System
• 15 Liver and Pancreas
• 16 Neuromuscular System
• 17 Endocrine System
• 18 Kidney and Urinary Bladder
• 19 Female Reproductive System
• 20 Male Reproductive System
• 21 Nervous System
• 22 Eye and Ear
• 23 Bones and Teeth
• Index
• End User License Agreement