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[P2.17]: Mecp2 and breathing symptoms in a mouse model of Rett Syndrome: On the trail of GABA involvement
Author(s) -
Voituron N.,
Menuet C.,
Lajard A.M.,
Hilaire G.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.147
Subject(s) - rett syndrome , mecp2 , citation , library science , gerontology , psychology , medicine , computer science , biology , genetics , gene , phenotype
models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory, core endophenotypes of schizophrenia. In humans, the SEMA6A gene and genes encoding the interacting proteins SEMA6B, PLXNA2 and PLXNA4 map to strong linkage peaks for schizophrenia and autism in isolated pedigrees. These findings are supported by association analyses, which we replicate and extend in the Irish population. Mice with mutations in Sema6A or the interacting genes represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. Of relevance to general mechanisms of neurodevelopmental pathogenesis, for example, we consider which of the physiological and behavioural phenotypes in these mutants may be associated with primary defects in circuitry, and which are more readily explained by secondary, network-level, reactive mechanisms, such as alterations in dopamine signalling. Finally, our biological data make these genes highly plausible candidates to explain the human linkage findings and suggest they may be directly involved in the etiology of psychiatric disorders.