Altered neocortical gene expression, brain overgrowth and functional over-connectivity in chd8 haploinsufficient mice

Philipp Suetterlin, Shaun Hurley, Conor Mohan, Kimberley L.H. Riegman, Marco Pagani, Angela Caruso, Jacob Ellegood, Alberto Galbusera, Ivan Crespo-Enriquez, Caterina Michetti, Yohan Yee, Robert Ellingford, Olivier Brock, Alessio Delogu, Philippa Francis-West, Jason P. Lerch, Maria Luisa Scattoni, Alessandro Gozzi, Cathy Fernandes, M. Albert Basson

Research output: Contribution to journalArticlepeer-review

Abstract

Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorder (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity, and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at midgestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the downregulated transcripts. Resting-state functional MRI identified increased synchronized activity in cortico-hippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioral phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that.

Original languageEnglish
Pages (from-to)2192-2206
Number of pages15
JournalCerebral Cortex
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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