ENU-mouse mutagenesis screen: In search of animal models of psychiatric disorders

Although a large number of knockout mutants will be engineered in the future, genetic analysis requires the availability of multiple alleles of the same gene or of different genes involved in the pathogenesis of the same disease. Such alleles can be obtained after treatment with chemical mutagens, such as Ethyl-nitrosourea (ENU) which is a powerful mutagen in mice. Complementary to the ‘gene-driven’ analysis of gene function, such ‘phenotype-driven’ approaches represent a rich resource for novel animal models for psychiatric disorders. This resource can only be used if efficient phenotyping assays are established. For behavioral phenotyping in mice we developed large-scale screening procedures to investigate a variety of behavioral dimensions. We identified mice which showed differential alterations restricted to specific cognitive processes, anxiety-related behavior, or locomotor activity, respectively. Using this hypothesis-free research strategy, we hope to identify novel candidate genes which are responsible for the control of pathological alterations in behaviors.