title: Closing the translational gap between mutant mouse models and the clinical reality of psychotic illness.
abstract: As animal models of psychotic illness become more refined, mutant mouse models have become increasingly prominent through their ability to inform on the structural, cellular and behavioural roles of genes associated with risk for psychosis via the phenotypic consequences of disruption of those genes. This review will consider recent advances in the field whereby mutant mouse models seek to reflect increasing knowledge of psychotic illness, focusing on four main themes. Firstly, recent GWAS and rare variant analyses have identified that disease-associated targets have not been previously implicated, thereby representing novel biological pathways in the illness, and this has implications for the modelling field. Secondly, the psychosis is disrespectful to conventional diagnostic boundaries, both clinically and in terms of pathobiology: it extends beyond schizophrenia to include several diagnostic categories and may be best captured in terms of psychopathological dimensions rather than/additional to such categories. Thirdly, a given risk gene (G) does not operate in isolation but, rather, appears to participate in complex interactions with environmental (E) risk factors, i.e., G×E interactions. Lastly, a given risk gene is likely to participate in complex, epistatic interactions with other risk genes, i.e., G×G interactions. Such studies constitute important steps in closing the translational gap between mutant mouse models and the clinical reality of psychotic illness.
authors.affiliation: School of Medicine, Brookfield Health Sciences Complex, University College Cork, Cork, Ireland. Electronic address: c.otuathaigh@ucc.ie.
authors.forename: Colm M
authors.initials: CM
authors.lastname: O'Tuathaigh
authors.affiliation: Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland; Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: John L
authors.initials: JL
authors.lastname: Waddington
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059647:Gene-Environment Interaction; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D011618:Psychotic Disorders / Q000235:genetics*; D057170:Translational Research, Biomedical
keywords: Gene–Gene interactions; Gene–environment interactions; Mutant mouse models; Mutant phenotype; Psychosis; Schizophrenia