TY - JOUR
T1 - Altered neocortical gene expression, brain overgrowth and functional over-connectivity in chd8 haploinsufficient mice
AU - Suetterlin, Philipp
AU - Hurley, Shaun
AU - Mohan, Conor
AU - Riegman, Kimberley L.H.
AU - Pagani, Marco
AU - Caruso, Angela
AU - Ellegood, Jacob
AU - Galbusera, Alberto
AU - Crespo-Enriquez, Ivan
AU - Michetti, Caterina
AU - Yee, Yohan
AU - Ellingford, Robert
AU - Brock, Olivier
AU - Delogu, Alessio
AU - Francis-West, Philippa
AU - Lerch, Jason P.
AU - Scattoni, Maria Luisa
AU - Gozzi, Alessandro
AU - Fernandes, Cathy
AU - Basson, M. Albert
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
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U2 - 10.1093/cercor/bhy058
DO - 10.1093/cercor/bhy058
M3 - Article
AN - SCOPUS:85047735670
VL - 28
SP - 2192
EP - 2206
JO - Cerebral Cortex
JF - Cerebral Cortex
SN - 1047-3211
IS - 6
ER -