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

Sahún, Ignasi; Marechal, Damien; Pereira, Patricia Lopes; Nalesso, Valérie; Gruart, Agnes; Garcia, José Maria Delgado; Antonarakis, Stylianos; Dierssen, Mara; Herault, Yann

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Title		Cognition and hippocampal plasticity in the mouse is altered by monosomy of a genomic region implicated in down syndrome
Authors		Sahún, Ignasi Marechal, Damien Pereira, Patricia Lopes Nalesso, Valérie Gruart, Agnes Garcia, José Maria Delgado Antonarakis, Stylianos Dierssen, Mara Herault, Yann show all authors [1 - 9]
Published in		Genetics. 2014, vol. 197, no. 3, p. 899-912
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.
Identifiers		DOI: 10.1534/genetics.114.165241 PMID: 24752061
Full text		Article (Published version) (987 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement
Research group		Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Citation (ISO format)		SAHÚN, Ignasi et al. Cognition and hippocampal plasticity in the mouse is altered by monosomy of a genomic region implicated in down syndrome. In: Genetics, 2014, vol. 197, n° 3, p. 899-912. https://archive-ouverte.unige.ch/unige:42272