Pathology of Laboratory Rodents and Rabbits

Stephen W. Barthold, Stephen M. Griffey, Dean H. Percy

• Publisher: Wiley-Blackwell
• Year: 2016
• ISBN:
  9781118924044
• Edition: 4
• Topic: Medicina
• Subtopic: Medicina veterinaria

Now in its fourth edition, Pathology of Laboratory Rodents and Rabbits has become a standard text for veterinary pathologists, laboratory animal veterinarians, students, and others interested in these species.

• The standard reference on the pathogenesis and cardinal diagnostic features of diseases of mice, rats, hamsters, gerbils, guinea pigs, and rabbits

• Expanded coverage of rabbit disease, normal anatomic features, and biology

• Over 450 color photographs illustrating gross and microscopic pathology

• Companion website offering images from the text in PowerPoint

1
Mouse

Introduction

Apart from the many inbred strains, substrains, spontaneous mutants, and outbred stocks of laboratory mice, the mouse has been, and continues to be, central to molecular genomics, with worldwide efforts continuing to “knock out” every functional gene in the mouse genome and define the relationship between genotype and phenotype. In addition to understanding the genome, various mouse strains and stocks, as well as the genetically engineered mouse (GEM), play critical roles in hypothesis-driven biomedical research. These trends have created rich opportunities and critical demand for comparative pathologists who are knowledgeable in mouse pathobiology. Unfortunately, the scientific literature is replete with erroneous interpretation of phenotype by scientists (as well as pathologists) lacking expertise in mouse pathology. Effective mouse pathology requires a global understanding of mouse biology, euphemistically termed “Muromics” (see Barthold 2002).

It is impossible for the pathologist to command in-depth knowledge of all strains, stocks, and mutant types of mice, and in many cases there is little baseline data to draw upon. Nevertheless, the mouse pathologist must be cognizant of general patterns of mouse pathology, as well as strain- and GEM-specific nuances. Recommended references (Frith & Ward, 1988; Maronpot et al. 1999; McInnes 2012; Mohr 2001; Mohr et al. 1996; Ward et al. 2000) provide thorough pictorial coverage of spontaneous mouse pathology in several common inbred strains of mice. The incidence and prevalence of strain-specific pathology are highly dependent upon genetic and environmental influences, including diet, bedding, infectious disease, age, sex, and other factors. Compared to the above-cited references, our coverage of the esoterica of spontaneous mouse pathology is relatively superficial. We herein emphasize general patterns of disease, while attempting to address important strain-, mutant-, and GEM-specific diseases when appropriate. There are a growing number of internet-accessible resources for mouse phenotyping and pathology of strains, stocks, and GEMs. A listing of these web resources is available through various sources (Bolon 2006; Brayton 2013; Fox et al. 2007, 2015). Although not specifically listed in this text, it is worth “surfing” through these cited websites that provide a plethora of information at multiple levels.

The unique qualities of the laboratory mouse and the precision of mouse-related research make infectious agents, even those with minimal (or no) pathogenicity, major concerns due to their potential and sometimes significant impact upon research reproducibility, including phenotype. A challenge that is unique to the mouse is the difficulty in drawing the line between commensalistic, opportunistic, or overtly pathogenic microorganisms. Since the last edition, a wide variety of immune-deficient GEMs have been created, thereby raising the status of several relatively innocuous infectious agents to the level of pathogens. Immune-deficient mice and new molecular methods of detection continue to reveal previously unrecognized mouse “pathogens,” such as a number of Helicobacter spp., norovirus, and most recently, astrovirus. Furthermore, the unrestricted traffic of GEMs among institutions and the pressure to reduce costs of maintenance at the expense of quality control have resulted in the re-emergence of several infectious agents that have not been seen in several decades. We, therefore, unabashedly emphasize mouse infectious diseases in this chapter. Despite advances in husbandry and diagnostic surveillance, we are reluctant to discard entities that may seem to have disappeared from laboratory mouse populations because of their likelihood of return.

Mouse Genetics and Genomics

The laboratory mouse is an artificial creation, and there is no true “wild-type” laboratory mouse. Furthermore, there is no such thing as “normal” microflora, since laboratory mice are often maintained in microbially pristine environments devoid of pathogens and opportunistic pathogens, as well as other commensal flora/fauna. Laboratory mice are largely derived from domesticated “fancy mice” that arose from many years of trading mouse variants among fanciers in Europe, Asia, North America, and Australia. The laboratory mouse genome is, therefore, a mosaic derived from different subspecies of the Mus musculus (house mouse) complex, including M.m. domesticus, M.m. musculus, M.m. castaneus, M.m. molossinus (a natural hybrid of M.m. musculus and M.m. castaneus), and others. The genome of M.m. domesticus is the predominant contributor to most strains of mice, but many inbred strains share a common “Eve” with a mitochondrial genome of M.m. musculus origin and a common “Adam” that contributed their Y chromosome from M.m. castaneus. In addition, there is evidence that other Mus species, outside of the M. musculus complex, have contributed to the genome of some, but not all, laboratory mouse strains. For example, the C57BL mouse genome contains a contribution from M. spretus. Perhaps the only laboratory mouse that is derived from a single M.m. domesticus species (subspecies) is the “Swiss” mouse. Several Mus species that are outside of the M. musculus complex, such as M. spretus, have been inbred. Thus, the laboratory mouse genome is not uniform among strains and mouse strains are not entirely within the M. musculus clade.

There are over 450 inbred strains of laboratory mice that have arisen during the last century, and these strains, which were selectively inbred to pan-genomic homozygosity for purposes entirely unrelated to modern research, are the foundation upon which literally thousands of spontaneous mutants and GEMs have been built. Additional inbred strains have been developed from wild mice (M.m. castaneus, M. spretus, etc.). Furthermore, “outbred” mice (mostly Swiss mice) are highly homozygous and nearly inbred. In addition to historical inbreeding that may be intentional or the inadvertent result of maintaining small populations of mice, rederivation of a mouse population results in genetic bottlenecks as well. There is no such thing as a truly “outbred” laboratory mouse with a fully heterozygous genome representative of wild-type M. musculus, and there is no wild mouse genetic counterpart of the laboratory mouse. Recently, an octaparental Diversity Outbred (DO) mouse stock was developed from eight disparately related inbred strains of mice, but this stock is not extensively utilized. When working with mice, the pathologist must also become facile with strains, substrains, sub-substrains, hybrids, congenics, insipient congenics, coisogenics, consomics, conplastics, recombinant inbreds, recombinant congenics, spontaneous mutants, random induced (radiation, chemical, retroviral, gene trap) mutants, transgenics (random insertions), and targeted mutant mice, each with relatively unique, predictable, and sometimes unpredictable phenotypes and patterns of disease whose expression is modified by environmental and microbial variables.

The inherent value of the laboratory mouse is its inbred genome, but maintaining th...

Table of contents

• Cover
• Title Page
• Copyright
• Preface
• About the Companion Website
• Chapter 1: Mouse
• Chapter 2: Rat
• Chapter 3: Hamster
• Chapter 4: Gerbil
• Chapter 5: Guinea Pig
• Chapter 6: Rabbit
• Index
• End User License Agreement