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Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2 Microdeletion Syndrome

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Simon Ro Nilsson, Kim Fejgin, Francois Gastambide, Miriam A Vogt, Brianne A Kent, Vibeke Nielsen, Jacob Nielsen, Peter Gass, Trevor W Robbins, Lisa M Saksida, Tine B Stensbøl, Mark D Tricklebank, Michael Didriksen, Timothy J Bussey

Original languageEnglish
Pages (from-to)3991-4003
Number of pages13
JournalCerebral cortex (New York, N.Y. : 1991)
Volume26
Issue number10
Early online date19 Sep 2016
DOIs
Publication statusE-pub ahead of print - 19 Sep 2016

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Abstract

A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome (22q11.2DS) may model the genetic basis of cognitive deficits relevant for neuropsychiatric disorders such as schizophrenia. To assess the models usefulness for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive battery of cognitive assays by partners within the NEWMEDS collaboration (Innovative Medicines Initiative Grant Agreement No. 115008). This battery included classic and touchscreen-based paradigms with recognized sensitivity and multiple attempts at reproducing previously published findings in 22q11.2DS mouse models. This work represents one of the most comprehensive reports of cognitive functioning in a transgenic animal model. In accordance with previous reports, there were non-significant trends or marginal impairment in some tasks. However, the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment was observed following more than 17 experiments and 14 behavioral paradigms. Thus - within the current protocols - the 22q11.2DS mouse model fails to mimic the cognitive alterations observed in human 22q11.2 deletion carriers. We suggest that the 22q11.2DS model may induce liability for cognitive dysfunction with additional "hits" being required for phenotypic expression.

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