Mouse mutagenesis and gene function

With the completion of the mouse and human genome sequences, a major challenge is the functional characterization of every gene within the mammalian genome. The mouse offers many advantages for the use of genetics to the study of human biology and disease. A variety of mouse mutagenesis technologies, either gene- or phenotype-driven, are used as systematic approaches. The availability of the mouse genome supports gene-driven approaches such as gene-trap and targeted mutagenesis in embryonic stem (ES) cells, allowing an efficiency and precision of gene disruption unmatched among other mammals. Furthermore, chemical and transposon mutagenesis of the mouse genome allows to perform phenotype-driven screens for the unbiased identification of phenotype–genotype correlations. These technologies already resulted in a collection of several thousand mutants. In this article on mouse mutagenesis and gene function, we present a comprehensive review of gene- and phenotype-driven mouse mutagenesis strategies. Besides a summary of the basic principles of each approach, we emphasize on the latest and future developments of mouse mutagenesis