Editorial [Hot Topic:Mammalian Mutant Resources for Therapeutic Challenges(Guest Editor: Koichiro Abe, Co-Guest Editors: Minoru Kimura & Ken-ichi Yamamura)]

After the publication of the draft human genome sequence, now complete or partial genome sequences of 25 mammalian species are available in public genome databases. Obviously, sequence comparisons among the species are crucial for identification of similarities and differences between humans and other mammals in genome evolution. In the post genomic era, however, attention has been paid to uncovering gene function and identifying gene products that might possess therapeutic value. Although, systems biology and in silico analysis will help to predict in vivo gene function in the future, genetic modification using model organisms are necessary to confirm the predictions experimentally in vivo. Because of experimental limitation in human, other mammalian models are essential for this purpose. The laboratory mouse (Mus musclus) has a long history as a human model in biomedical research since early days of genetics. For most of the 20th century, production, identification, and analysis of mouse mutant strains were carried out independently in small scale. During this period, the spontaneous or induced mutant strains were archived and maintained by individual institution or scientist. Through the development of transgenic and gene targeting techniques in mice, the situation changed dramatically. The number of scientists working with mice rapidly increased. Engineering of mouse genome attracted many molecular biologists, because it seemed the most efficient way to study functions of gene in vivo and to generate models for human diseases. During same period, several large integrated projects were undertaken. They include the sequencing of the mouse genome, the production of numerous new mutations using chemical mutagens or by gene trap, and systematic phenotyping of many inbred and mutant strains. Despite the large body size and technical inabilities, chemical mutagenesis projects in rats are in progress. The resources also contain increased number of genetically engineered mutants and gene targeted ES clones from the knockout mouse project, which is a high-throughput international effort to produce knockout ES cells for all mouse genes. These precious and valuable resources, however, are not connected to efficient systems to produce novel therapeutic strategies or drug development. In this special issue of Current Pharmaceutical Biotechnology, we aimed to enhance and increase interaction between the mammalian mutant resource projects and pharmaceutical science. For this purpose, we selected three categories for review articles: 1) introduction of mammalian resource projects; 2) technology aspects for developing the resources; 3) applications of the mammalian resources to human diseases. First, chemically induced mutant resources are described; Soewarto et al. and Mashimo & Serikawa reviewed recent progress of ethyl nitrosourea (ENU) mutagenesis projects in the mouse and the rat, respectively. Araki et al. introduced ES cell based gene-driven mutagenesis projects, the gene trap project, and the usage of web-based database to obtain the information on trapped clones. Matsushima introduces that genetic variation in wild mice derived strains is also a valuable source for mutations. In addition to these four reviews on mutant resources, two reviews were selected to expand on technological usage of mutant resources. Fuchs et al. described the German Mouse Clinic, a large phenotyping centre for mutant mice, and its output. The standardization of the phenotyping is becoming more and more important in order to share phenotype information in the future. Ohtsuka et al. focused on recent progress and improvement on techniques in DNA construction for genetic engineering. The developing techniques are critical for production of genetically engineered animals in a highthroughput manner. Finally, usages and application of the mutant resources for human disease are described. Abe & Yu reviewed a positional cloning strategy for mutant strains with inflammatory arthritis. Miyamoto et al. focused on analysis of genetic engineered mice for preclinical studies. Many examples show that mutants of experimental animals are used as in vivo confirmation for pathogenesis of human diseases. More frequently, aspects from analysis of various mammalian mutants could be applied to development of new treatments and drugs in next decades. Thus mammalian mutant resources hold vast potential to accelerate the novel therapeutic challenges and thereby contribute to human health. We hope that this issue helps to the bridging and development of the interaction among different fields for the aspiration.