In the field of neurobiology and behavior, screening of ENU mutagenized mice will yield novel disease-relevant genes and pathways, as well as therapeutic and diagnostic targets for neurological and psychiatric disorders. Ingenium employs one of the largest recessive mutagenesis programs worldwide, in which all genetic variants are thoroughly characterized by a high throughput screen battery, including neurological and behavioral tasks. To screen for mouse models of psychiatric disorders, tests for anxiety-, schizophrenia-, depression- and cognition-related behaviors are implemented into the screen. Established test systems, like the Dark-Light Box, Elevated-Plus-Maze and Open-Field, are performed using fully automated video tracking for the detection of abnormal, anxious or explorative behavior. The Prepulse Inhibition of the Acoustic Startle Reflex has been assessed as a measure of sensorimotor gating, which is defective in schizophrenia patients. Depression-like symptoms are screened by the Tail Suspension and Porsolt Forced Swim tasks. Finally, cognition is tested using Fear Conditioning and Passive Avoidance, the most straightforward assays to study learning and memory deficits.

Beside the behavioral paradigms, the screen includes a broad set of neurological tasks, testing motor coordination, muscular functions and sensory functions, including assessment of hypo- and hyperalgesia. As pieces of the diagnostic puzzle, all major clinical chemistry parameters, blood cell counts and a broad variety of immunological parameters are generated for every mouse in the primary screen.

Secondary assays consist of measurement of activity, circadian activity patterns and cognition tests. Thorough neuropathological analyses of the CNS, PNS and muscular system are also indispensable as a secondary assay. Our comprehensive screen, determined by repeated and secondary analyses, confirms recessive neurological or behavioral phenotypes in about 5% of the investigated animals. More than 50% are immediately genetically confirmed by the presence of at least two phenotypically identical animals per pedigree. Several mouse lines will be detailed in the areas of anxiety-, hyperactivity- and schizophrenia-related disorders.

Paper presented at Measuring Behavior 2002 , 4^th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands

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