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| Status |
Public on Jun 21, 2017 |
| Title |
Germline Chd8 haploinsufficiency alters brain development in mouse |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
We examined the impact of germline heterozygous frameshift Chd8 mutation on neurodevelopment in mice. Adult Chd8+/del5 mice exhibited cognitive impairment correlated with increased cerebral cortex, hippocampus, and amygdala volume, but displayed normal social interactions and no repetitive behaviors. Network analysis of neurodevelopmental gene expression revealed widespread transcriptional changes in Chd8+/del5 mice across pathways disrupted in neurodevelopmental disorders, including neurogenesis, synaptic processes, and neuroimmune signaling. Among gene co-expression networks, we identified a module with peak expression in early brain development that featured dysregulation of genes enriched for promoter binding by Chd8 and associated with RNA processing, chromatin remodeling, and cell cycle. We validated increased neuronal proliferation and splicing alterations during Chd8+/del5 brain development. Our results show that Chd8+/del5 mice exhibit neurodevelopmental changes paralleling humans with CHD8 mutations and highlight widespread pathological consequences of Chd8 haploinsufficiency.
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| Overall design |
We examined RNA expression (RNA-sequencing) and Chd8 binding to the genome (ChIP-seq) from whole forebrain dissections of WT and germline heterozygous Chd8 mutant mice.
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| Contributor(s) |
Gompers AL, Su-Feher L, Ellegood J, Copping NA, Riyadh MA, Stradleigh TW, Pride MC, Schaffler MD, Wade AA, Catta-Preta R, Zdilar I, Louis S, Kaushik G, Mannion BJ, Plajzer-Frick I, Afzal V, Visel A, Pennacchio LA, Dickel DE, Lerch JP, Crawley JN, Zarbalis KS, Silverman JL, Nord AS |
| Citation(s) |
28671691 |
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| Submission date |
May 25, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Alex Nord |
| E-mail(s) |
[email protected]
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| Phone |
530-754-5022
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| Organization name |
University of California Davis
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| Department |
Neurobiology, Physiology, and Behavior
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| Street address |
1544 Newton Court
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| City |
Davis |
| State/province |
CA |
| ZIP/Postal code |
95618 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA388479 |
| SRA |
SRP108291 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99331_Gompers_logRPKM_Matrix.txt.gz |
2.9 Mb |
(ftp)(http) |
TXT |
| GSE99331_RAW.tar |
414.4 Mb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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