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  4. Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation.
 
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Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation.
File(s)
2017 Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation..pdf (1.15 MB)
Published version
Author(s)
Benevento, Marco
Oomen, Charlotte A
Horner, Alexa E
Amiri, Houshang
Jacobs, Tessa
more
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
URI
http://hdl.handle.net/10044/1/57122
DOI
https://www.dx.doi.org/10.1038/srep40284
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
7
Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The images
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
License URL
http://creativecommons.org/licenses/by/4.0/
Identifier
PII: srep40284
Publication Status
Published
Article Number
40284
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