Abstract
Pathologists working with genetically engineered mice (GEM) often feel they are continually being faced with variations on the theme of “mouse.” These variations can include not only the phenotypic changes produced by transgenes and targeted mutagens but also the unusual lesions that can be induced in these GEMs when infected by normal lab animal diseases. We often have to remind investigators that changes can occur both as a direct result of transformations at the intended target locus/gene and less predictably as a result of how the remaining DNA is read. Thus, detailed phenotypic evaluations are needed to characterize all the results of genetic manipulations both in the disease-free GEM and in those affected by the usual and unusual lab animal diseases.
The popularity of GEMs has led to the use of core facilities where investigators can almost order the mutation they desire and to the presence of these mice in just about every major lab animal facility throughout the world. As such, even veterinary pathologists who have not been involved with the development of these mice now find themselves doing phenotypic characterizations, if only on a diagnostic basis. Lab animal diseases are now manifesting themselves in ways never reported before and are more frequent and often more severe. Pathologists must be aware of not only the natural lesions of the base strains used in making the GEMs but also of the pathology associated with specific genetic changes. References, however, have been few, and it has been necessary to scour the journals for case reports and articles related to this field. As new editions of lab animal medicine and pathology books are published, they are including information on these GEMs but this is rarely extensive. The Pathology of Genetically Engineered Mice is a new text and the first volume devoted exclusively to the pathology of these GEMs. The editors have assembled material derived from presentations given at the symposium “The Pathology of Genetically Engineered Mice” held at the National Institutes of Health in 1999. This 394-page book includes a preface on Mutant Mouse Resources and is divided into four sections entitled “Techniques,” “Embryos,” “General Pathology,” and “Special Pathology.” Important general mouse pathology and biology references and mouse information websites are listed at the end. I particularly appreciated the unusual feature of also referencing pertinent websites in the text itself. Visually, the book is a pleasure to peruse. There are over 200 illustrations, almost all of which are in color and include not only gross and microscopic pathology (the quality of which is excellent) but also color diagrams, phosphor imaging, flow cytometry, and laser capture microdissection. There are some of the best illustrations on the development and histology of the mouse placenta I have ever come across, as well as an extensive series of stained whole brain sections. The book reads well, although the style varies somewhat among chapter authors. The sections and subheadings, however, are standardized for all chapters and make this book easy to use. Although the subheadings seem to be in an overly large bold type, the subsections are clearly identified.
The first chapter presents the role of the repository in maintaining and distributing genetically engineered strains of mice and the resources supporting their use. The “Techniques” section is a review of the methods applicable to creating and evaluating GEMs and includes such topics as in situ hybridization, phosphor storage imaging, immunohistochemistry, confocal microscopy, and measurements of apoptosis. The “Embryo” section includes methods of handling, viewing, and evaluating mouse embryos and detailed illustrations of placental development and full body sections. Other chapters cover brain development, gene discovery, and gestational mortalities in GEMs.
The “General” and “Special Pathology” sections review the genetic background lesions of the more commonly used mouse strains and how to do a phenotypic evaluation on a GEM. Tables of neoplastic and nonneoplastic lesions supplement the background strain descriptions, which could be a bit more extensive. Specific lesions of the skin, eye, brain, kidney, reproductive, and gastrointestinal systems are well described, and strategies for behavioral phenotyping and classifying lymphomas are also reviewed. The photomicrographs for the system chapters are of excellent quality and illustrate well the important pathologic changes. It is hoped that similar chapters on the systems not covered will be added in the next edition of this book. The book seems well indexed. I randomly opened the book at a dozen pages; all items contained in those pages were in the index. In fact, there is even a separate “Numbers” category listed in the index.
This book should prove tremendously valuable to veterinary pathologists who work with these mice and to those who desire a guide to evaluating GEMs and a reference to their pathology. Molecular biologists and scientists involved with GEMs should find this book invaluable, providing a source of methodology, pertinent websites, and up-to-date references. The clear structure, tables, and color illustrations make the book attractive and accessible.