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Following the genes: a framework for animal modeling of psychiatric disorders

Kevin J Mitchell1*, Z Josh Huang2, Bita Moghaddam3 and Akira Sawa4

Author Affiliations

1 Smurfit Institute of Genetics and Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland

2 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

3 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA

4 Department of Psychiatry and Behavioral Sciences and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

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BMC Biology 2011, 9:76  doi:10.1186/1741-7007-9-76

Published: 11 November 2011

Abstract

The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. Defining the underlying pathogenic mechanisms will require an experimental and theoretical framework to make the links from mutation to altered behavior in an animal or psychopathology in a human. Here, we discuss key elements of such a framework, including cell type-based phenotyping, developmental trajectories, linking circuit properties at micro and macro scales and definition of neurobiological phenotypes that are directly translatable to humans.

Keywords:
autism; schizophrenia; rare mutations; synaptic; interneurons; EEG; functional connectivity; microcircuits; Cre; allelic heterogeneity