The role of mutagenesis in defining genes in behaviour

The study of human behavioural and psychiatric disorders benefits from the development of genetic models in mice and other organisms. Mouse mutants allow one to investigate the molecular basis of disease progression and to develop novel therapies. The number of potential mouse models is increasing dramatically through the implementation of mutagenesis screens for aberrant behavioural phenotypes. The alkylating agent N-ethyl-N-nitrosourea ENU is the mutagen of choice in these screens as it induces mutations at a very high rate. Progeny of chemically-mutagenised animals are screened either in systematic high-throughput test batteries or in specific low-throughput tests. Both approaches have been highly successful with large numbers of novel loci being identified and characterised. Many mutant lines are available for general research with phenotypes and genetic map positions on public websites. Of the mutant genes characterised, the majority have contributed to our knowledge of gene function in physiology and disease. The 'mutagenesis screening' approach continues to evolve through the design of new phenotyping strategies. The development of modifier screens in mice shows promise in the elucidation of complex phenotypes whereas the use of mutagenesis in combination with pharmacological agents targets specific neurochemical systems. Finally, the systematic screening approach has demonstrated that mutations are likely to affect more than one biological process.