MUTANT MOUSE: bona fide Biosimulator for the Functional Annotation of Gene and Genome Networks

The advancements of genomics and genome projects led to the current paradigm that the blueprint of life is depicted in the genome sequences. To decipher the life system, deductive methods have been applied from genome sequences to genes, transcripts, proteins, organelles, cells, tissues, organs, organisms, and populations. As a result we encountered an astronomical scale of complicated molecular and cellular networks in the life system. There is a way, however, to directly connect the function of a single base pair (bp) in genome sequences to the life system by bypassing all the molecular and cellular labyrinths. “MUTANT” provides the ultimate tool as a bona fide biosimulator for the functional annotation of gene and genome networks. Genetics, with mutations and mutants, is revealing the life system. Mendel deduced the concept of “gene” from a large dataset of the pea phenome. Snell discovered the mouse H2 locus by graft rejection that led to the identification and understanding of the major histocompatibility complex. Many other mouse mutants (i.e., nu, scid, lpr, gld, Sl, and W) provided model systems for the functional characterization of key genes in immunological networks. In this context, “reverse genetics” methods have been developed since the 1980s to systematically produce mutant mice carrying a particular gene of interest, for example, transgenic mice, knockout mice, and gene targeting. Recently, more versatile, large-scale, and high-throughput methods such as ENU mutagenesis and insertional mutagenesis are being used to generate mutant mice. This chapter offers a review of the history and current status of mouse mutagenesis and discusses the value of mouse model systems.