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Haploinsufficiency of EHMT1 improves pattern separation and increases hippocampal cell proliferation

Research output: Contribution to journalArticle

  • Marco Benevento
  • Charlotte A. Oomen
  • Alexa E. Horner
  • Houshang Amiri
  • Tessa Jacobs
  • Charlotte Pauwels
  • Monica Frega
  • Tjitske Kleefstra
  • Maksym V. Kopanitsa
  • Seth Grant
  • Timothy J Bussey
  • Lisa M Saksida
  • Catharina E.E.M. Van der Zee
  • Hans van Bokhoven
  • Jeffrey C. Glennon
  • Nael Nadif Kasri

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Original languageEnglish
JournalScientific Reports
Early online date10 Jan 2017
Publication statusE-pub ahead of print - 10 Jan 2017


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.

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