Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation.
Author(s)
Type
Journal Article
Abstract
Heterozygous mutations or deletions of the human Euchromatin Histone Methyltransferase 1 (EHMT1) gene are the main causes of Kleefstra syndrome, a neurodevelopmental disorder that is characterized by impaired memory, autistic features and mostly severe intellectual disability. Previously, Ehmt1+/-heterozygous knockout mice were found to exhibit cranial abnormalities and decreased sociability, phenotypes similar to those observed in Kleefstra syndrome patients. In addition, Ehmt1+/-knockout mice were impaired at fear extinction and novel- and spatial object recognition. In this study, Ehmt1+/-and wild-type mice were tested on several cognitive tests in a touchscreen-equipped operant chamber to further investigate the nature of learning and memory changes. Performance of Ehmt1+/-mice in the Visual Discrimination &Reversal learning, object-location Paired-Associates learning- and Extinction learning tasks was found to be unimpaired. Remarkably, Ehmt1+/-mice showed enhanced performance on the Location Discrimination test of pattern separation. In line with improved Location Discrimination ability, an increase in BrdU-labelled cells in the subgranular zone of the dentate gyrus was observed. In conclusion, reduced levels of EHMT1 protein in Ehmt1+/-mice does not result in general learning deficits in a touchscreen-based battery, but leads to increased adult cell proliferation in the hippocampus and enhanced pattern separation ability.
Date Issued
2017-01-10
Date Acceptance
2016-12-02
Citation
Scientific Reports, 2017, 7
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
7
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© The Author(s) 2017
or other third party material in this article are included in the article’s Creative Commons license,
unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
license, visit http://creativecommons.org/licenses/by/4.0/
© The Author(s) 2017
Copyright URL
Identifier
PII: srep40284
Publication Status
Published
Article Number
40284