S.02.02 Developmental models of schizophrenia and their behavioural characterisation

Abstract

This presentation reviews the application of mutant mouse phenotypes to the study of neuropsychiatric disorders in general and psychotic illness in particular, with schizophrenia as the primary exemplar. It considers these issues at the levels of behavioural, psychopharmacological and cellular phenotypes of putative import for understanding disease processes and drug development. Mutant models appear to be heuristic at two main levels; firstly, by indicating the functional roles of neuronal components thought to be of relevance to the putative pathobiology of psychotic illness, they help resolve overt behavioural and underlying cellular processes regulated by those neuronal components; secondly, by indicating the functional roles of genes associated with risk for psychotic illness, they help resolve overt behavioural and underlying cellular processes regulated by those risk genes. This presentation focusses initially on models of dopaminergic and glutamatergic dysfunction. Then, it considers advances in the genetics of schizophrenia and mutant models relating to replicable risk genes. There is continuing need to address not only numerous technical challenges but also to develop more ‘real world’ paradigms that reflect the milieu of gene × environment and gene × gene interactions that characterise psychotic illness and its response to antipsychotic drugs. Thus, the presentation extends this discussion by exemplifying two new, variant approaches in mutant mice that may serve as prototypes for advancing understanding of disease processes and drug development. An enduring challenge is the translational relationship between mouse phenotype, clinical psychopathology and, to the extent known, disease pathobiology. S.02.02 Developmental models of schizophrenia and their behavioural characterisation