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Cognition and hippocampal plasticity in the mouse is altered by monosomy of a genomic region implicated in Down syndrome. | LitMetric

Cognition and hippocampal plasticity in the mouse is altered by monosomy of a genomic region implicated in Down syndrome.

Genetics

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 67404 Illkirch, France Centre National de la Recherche Scientifique, UMR7104, Illkirch, France Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France Université de Strasbourg, 67400 Illkirch, France Institut Clinique de la Souris, PHENOMIN, Groupement d'Intérêt Economique Centre Européen de Recherche en Biologie Moléculaire, 67404 Illkirch, France

Published: July 2014

AI Article Synopsis

Article Abstract

Down syndrome (DS) is due to increased copy number of human chromosome 21. The contribution of different genetic regions has been tested using mouse models. As shown previously, the Abcg1-U2af1 genetic region contributes to cognitive defects in working and short-term recognition memory in Down syndrome mouse models. Here we analyzed the impact of monosomy of the same genetic interval, using a new mouse model, named Ms2Yah. We used several cognitive paradigms and did not detect defects in the object recognition or the Morris water maze tests. However, surprisingly, Ms2Yah mice displayed increased associative memory in a pure contextual fear-conditioning test and decreased social novelty interaction along with a larger long-term potentiation recorded in the CA1 area following stimulation of Schaffer collaterals. Whole-genome expression studies carried out on hippocampus showed that the transcription of only a small number of genes is affected, mainly from the genetic interval (Cbs, Rsph1, Wdr4), with a few additional ones, including the postsynaptic Gabrr2, Gabbr1, Grid2p, Park2, and Dlg1 and the components of the Ubiquitin-mediated proteolysis (Anapc1, Rnf7, Huwe1, Park2). The Abcg1-U2af1 region is undeniably encompassing dosage-sensitive genes or elements whose change in copy number directly affects learning and memory, synaptic function, and autistic related behavior.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096369PMC
http://dx.doi.org/10.1534/genetics.114.165241DOI Listing

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