Journal Article

Reduced Expression of STOP/MAP6 in Mice Leads to Cognitive Deficits

Julien Volle, Jacques Brocard, Mohamed Saoud, Sylvie Gory-Faure, Jérôme Brunelin, Annie Andrieux and Marie-Françoise Suaud-Chagny

in Schizophrenia Bulletin

Published on behalf of Maryland Psychiatric Research Center

Volume 39, issue 5, pages 969-978
Published in print September 2013 | ISSN: 0586-7614
Published online September 2012 | e-ISSN: 1745-1701 | DOI: http://dx.doi.org/10.1093/schbul/sbs113

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Background: STOP/MAP6 null (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP null mice. Methods: Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals raised either in standard conditions (controls) or submitted to maternal deprivation. Results: Control Het mice displayed prominent deficits in social interaction and learning, resembling KO mice. In contrast, they exhibited short-lasting locomotor hyperreactivity to acute mild stress and no impaired locomotor response to amphetamine, much like WT mice. Additionally, perinatal stress deteriorated Het mouse phenotype by exacerbating alterations related to positive symptoms such as their locomotor reactivity to acute mild stress and psychostimulant challenge. Conclusion: Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities. Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.

Keywords: schizophrenia; animal model; microtubule; neurodevelopment; behavioral phenotype; gene x environment interaction

Journal Article.  5514 words.  Illustrated.

Subjects: Child and Adolescent Psychiatry

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