Abstract

Genetic and biomarker studies in patients have identified the Neural Cell Adhesion Molecule (NCAM) and its associated polysialic acid (PSA) as a susceptibility factors for schizophrenia. NCAM and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations. Indeed, various schizophrenia-relevant morphological, cognitive and emotional deficits have been observed in these mutants. Here we studied social interaction and attention of NCAM null mutant (NCAM−/−) mice as further hallmarks of schizophrenia. Nest building, which is generally associated with social behavior in rodents, was severely impaired, as NCAM−/− mice continuously collected smaller amounts of nest building material than their wild type littermates and built nests of poorer quality. However, social approach tested in a three—compartment—box was not affected and latent inhibition of Pavlovian fear memory was not disturbed in NCAM−/− mice. Although NCAM deficient mice do not display a typical schizophrenia-like phenotype, they may be useful for studying specific endophenotypes with relevance to the disease.

Highlights

  • Genetic linkage and association studies suggest a polygenetic contribution of multiple risk genes that influence the susceptibility to develop schizophrenia (Gejman et al, 2011)

  • Neural Cell Adhesion Molecule (NCAM) and polysialtransferase mutant mice have been generated that may serve as animal models for this disorder and allow to investigate underlying neurodevelopmental alterations

  • Nest quality was rated after paper tissue was provided directly in the cage (N = 6 for NCAM−/−; N = 7 for NCAM+/+) to control for potential differences related to the nesting material or material gathering

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Summary

Introduction

Genetic linkage and association studies suggest a polygenetic contribution of multiple risk genes that influence the susceptibility to develop schizophrenia (Gejman et al, 2011). Single gene mutations are thought to contribute to less 0.1% to the heritability of schizophrenia. Mice with genetic manipulations of identified susceptibility genes may provide valuable tools for better understanding the neurobiology of schizophrenia and the development of new therapeutic strategies. Testing of endophenotypes related to schizophrenia in animal models generally is focused on deficits in cognition, attention, and negative symptoms like emotional blunting or social dysfunction (Kellendonk et al, 2009; Mazzongini et al, 2009; Amann et al, 2010). The analysis of morphological changes in such rodent models has provided strong support for the neurodevelopmental hypothesis of schizophrenia (Robertson et al, 2006; Jaaro-Peled et al, 2010; Lu et al, 2011)

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