Monica Justice and Mary Bedell (Eds): Mutagenesis of the Mouse Genome

Abstract

Mutagenesis of the Mouse Genome Monica Justice and Mary Bedell (eds) Kluwer Academic Publishers, 2004. $138.00, 97 pp. ISBN 1-4020-2875-X Mutagenesis of the Mouse Genome is a collection of papers originally presented at the Second Georgia Genetics Symposium in 2002 and printed in a special issue of Genetica in 2004. The volume opens with a wonderful, lovingly written tribute to the work of the late Dr William L. Russell and a history of mouse genetics at Oak Ridge National Laboratory, along with much information about the origins of mouse mutagenesis in relation to both human and mouse genomics. In each of the chapters that follow, a specific aspect of chemical mutagenesis and its applications are presented. Guenet presents a valuable survey of experimental mutagenesis strategies, including balancer and gene targeting strategies, preserving the history of mutant lines that are available for use today. This chapter highlights the pros and cons of N-ethyl-N-nitrosourea (ENU) mutagenesis and discusses the importance of allelic series, a point emphasized in a subsequent chapter by Meisler et al. which illustrates and elaborates on the range and variety of neurological deficiencies discovered in an allelic series of Scn8a. This is an especially relevant discussion as a counterpoint to knockout strategies, which are not covered in this book. Russell's chapter describes the importance of the single locus test, and presents an analysis of mutation frequency induced by various mutagens at several phases of sperm development. This chapter is also chock full of important historical information and background on the existing ENU lines. Two chapters are devoted to the major mutagenesis screens and, of interest to readers of G2B, they detail the wealth of neurobehavioral traits that have been evaluated in phenotype-driven strategies. Information for finding the resulting novel mutant mouse resources is also provided. Each of these chapters highlights the importance, progress and challenge in mapping the relevant mutations to a specific locus. The chapter by Beier and Herron suggests a strategy that can greatly facilitate localization of mutations for highly penetrant effects. It is not clear whether this approach will work for the complex, polygenic phenotypes of interest to many neuroscientists. However, several other chapters are devoted to the complexity of gene by gene and gene by environment interactions in mutant analysis, including Meisler et al.'s discussion of the positional cloning of an Scn8a modifier locus that varies among inbred strains and an excellent chapter by Barthold that highlights the numerous sources of confounds and environmental interactions that can vex users of mutant resources. The Mouse Phenome Database, a resource of phenomenal value for evaluating phenotypic differences among standard inbred strains was also described, although in this context, I would have liked to read more about its application for mutant analysis. A concluding chapter by Eppig describes many of the mutant database resources and highlights challenges to data management for complex mutagenesis projects. In summary, this volume collects in one place much information that will prove valuable to current and prospective users of the wealth of mice produced by chemical mutagenesis. The history, origins, utility, complexity, phenotypic diversity, mutation rate analyses, background effects, mapping and interpretational issues are all nicely summarized by individuals with tremendous experience in this field. However, on this long flight, I found myself wishing for more of it! At a mere 97 pages, many of these issues were mentioned only in passing. Other current issues were intentionally omitted to maintain focus, notably including knockout methods. Also omitted was a discussion of quantitative issues beyond mutation rate, and these issues have a very important role in the success of balancer strategies and mutant detection. I would have greatly enjoyed an integrative summary or concluding remarks as this approach to mouse resource development transitions into the ‘post-genome’ era. The restricted focus and high price may limit the appeal of the book to those who are either actively engaged in mutagenesis or who are interested in using the wealth of mutant mouse resources to their research program. For these readers, there awaits a treasure trove of information on the somewhat arcane origins of these important mice. Such details are often lost to young and future scientists. Mutants have been identified for hundreds of brain and behavioral phenotypes, and this book provides a strong introduction to the origins, acquisition and use of mutagenized mice. Elissa J. Chesler † † Oak Ridge National Laboratory Bldg. 1061, MS-6445 PO Box 2008 Oak Ridge, TN 37831-6445 USA E-mail: cheslerej@ornl.gov