New insights into behaviour using mouse ENU mutagenesis

Identifying genes involved in behavioural disorders in man is a challenge as the cause is often multigenic and the phenotype is modulated by environmental cues. Mouse mutants are a valuable tool for identifying novel pathways underlying specific neurological phenotypes and exploring the influence both genetic and non-genetic factors. Many human variants causing behavioural disorders are not gene deletions but changes in levels of expression or activity of a gene product; consequently, large-scale mouse ENU mutagenesis has the advantage over the study of null mutants in that it generates a range of point mutations that frequently mirror the subtlety and heterogeneity of human genetic lesions. ENU mutants have provided novel and clinically relevant functional information on genes that influence many aspects of mammalian behaviour, from neuropsychiatric endophenotypes to circadian rhythms. This review will highlight some of the most important findings that have been made using this method in several key areas of neurological disease research.