Mouse Phenotypes — A Handbook of Mutation Analysis

  • Virginia E. Papaioannou &
  • Richard R. Behringer
Cold Spring Harbor Laboratory Press • 2005 USD 80/GBP 59

So you want to know how to create a mouse with a mutation in your favourite gene? Or maybe you already have such a line and you need to maintain it and explore its phenotype? Where do you start? Fear not, because help is at hand in the form of a new practical manual: Mouse Phenotypes — A Handbook of Mutation Analysis, written by Virginia Papaioannou and Richard Behringer. Whether you have years of experience, or whether this is your first foray into the world of the mutant mouse, this is the book for you.

The inspiration for this text comes from the authors' firsthand experience of teaching the Molecular Embryology of the Mouse course at Cold Spring Harbour Laboratory, and this is apparent in its logical approach to analysis of mouse phenotypes. With its simple protocols, clear and concise scientific explanations and informal advice, this book should enable any scientist to analyse most mouse phenotypes in a step-by-step manner. Although this is not the first book to be written on this subject, it is more user friendly than several previous books, and we certainly wished that it had existed when we first entered the world of mouse gene targeting.

The book begins with instructions on how to obtain a mutant mouse, outlining various gene-targeting strategies, whilst carefully pointing out the pros and cons of each. It also gives specific tips and realistic timescales for all stages of the process. The authors outline each step, from designing gene targeting constructs, through embryonic stem cell targeting to the generation of chimeric offspring. They also offer advice on breeding strategies for identifying mutant phenotypes and on maintaining the mutant mouse line that you will, by now, have devoted much time and effort into generating.

If, on the other hand, you already have your mouse of interest, then you can fast-track to chapter five where the phenotypic analysis begins. This is where the book really comes into its own, giving detailed information and protocols for analysis of any kind of phenotype, regardless of the timing of lethality. Special emphasis is given to investigating mutations that affect early embryonic development. There is also a wealth of information to help assess whether the phenotype shown by a mutant is dominant or semi-dominant, in addition to advice about the common problems associated with both. Finally, should your mutant have an early lethality phenotype, there is an entire chapter dedicated to finding ways around this potentially frustrating phenomenon. Many of us know all too little about the early development of the mouse and how useful this information can be in discovering more about the function of our favourite gene(s).

This 235-page ring-bound text is extremely accessible to both the beginner and the expert. It is well organized into eight clearly defined chapters and three appendices, which can be viewed either as a logical progression through the generation and analysis of mutant mice, or dipped into by the more experienced reader to extract specific information on any given point of interest. Useful information boxes that are interspersed throughout the text, together with appropriate illustrations and signposting to other relevant sections, make up for the lack of detail in some chapters. However, for protocols on the subject of assisted reproduction such as superovulation, the reader is referred to Manipulating the Mouse Embryo: A Laboratory Manual (CSHL Press, 2003). This second book also becomes a source for protocols on the cryopreservation of sperm and embryos, and on embryo culture. Similarly, recipes for reagents used during in situ hybridization, whole-mount staining and sectioning, are all contained within this second text. It is therefore essential that the reader has access to both texts to maximize the benefit gained from the information contained within the chapters on analysing pre- and postnatal phenotypes.

The reader is also pointed to a whole host of additional books and resources in appendix one. This list in itself will be of tremendous value to those starting out. Appendix two provides published examples of phenotypic analysis and specific techniques, and a glossary of terms in appendix three will prove invaluable to those new to any of the topics covered within this text. The book would, however, benefit from additional appendices containing at least the basic in situ hybridization and whole-mount staining recipes, in addition to some of the most common assisted reproduction procedures.

This text contains an abundance of information and resources on all aspects of mutant mouse generation and analysis in one invaluable volume. At present, too many mouse phenotypes are going unnoticed, but this book will certainly help to redress the balance. Any laboratory whose work involves the generation and analysis of mutant mice should have at least one copy of this book.