PERFORM Publications

Title:	Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits.
Authors:	Tamming RJ , Dumeaux V , Jiang Y , Shafiq S , Langlois L , Ellegood J , Qiu LR , Lerch JP , Bérubé NG
Link:	https://www.ncbi.nlm.nih.gov/pubmed/32610139?dopt=Abstract
DOI:	10.1016/j.celrep.2020.107838
Category:	Cell Rep
PMID:	32610139
Dept Affiliation:	PERFORM 1 Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Biochemistry, Western University, London, ON, Canada. 2 Department of Paediatrics, Western University, London, ON, Canada; PERFORM Centre, Concordia University, Montreal, QC, Canada. 3 Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada. 4 Children's Health Research Institute, London, ON, Canada; Department of Paediatrics, Western University, London, ON, Canada; Department of Anatomy & Cell Biology, Western University, London, ON, Canada. 5 Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Anatomy & Cell Biology, Western University, London, ON, Canada. 6 Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada. 7 Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, The University of Oxford, Oxford, UK. 8 Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, The University of Toronto, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, The University of Oxford, Oxford, UK. 9 Children's Health Research Institute, London, ON, Canada; Lawson Health Research Institute, London, ON, Canada; Department of Paediatrics, Western University, London, ON, Canada; Department of Anatomy & Cell Biology, Western University, London, ON, Canada; Department of Oncology, Western University, London, ON, Canada. Electronic address: nberube@uwo.ca.

Description:

Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits.

Cell Rep. 2020 Jun 30;31(13):107838

Authors: Tamming RJ, Dumeaux V, Jiang Y, Shafiq S, Langlois L, Ellegood J, Qiu LR, Lerch JP, Bérubé NG

Abstract

ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the suppressive histone mark H3K27me3 is significantly reduced upon the loss of ATRX. We conclude that the ablation of ATRX in excitatory forebrain neurons leads to sexually dimorphic effects on miR-137 expression and on spatial memory, identifying a potential therapeutic target for neurological defects caused by ATRX dysfunction.

PMID: 32610139 [PubMed - as supplied by publisher]

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