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| Status |
Public on Mar 26, 2019 |
| Title |
Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioural and myelin alterations rescuable by a remyelinating drug [human] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Williams syndrome (WS), caused by a heterozygous microdeletion in 7q11.23, is a neurodevelopmental disorder characterized by hypersociability and neurocognitive abnormalities. Of the deleted genes, general transcription factor II-i (Gtf2i) has been linked to hypersociability in WS, though the underlying mechanisms are poorly understood. We show that selective deletion of Gtf2i in forebrain excitatory neurons caused neuroanatomical defects, fine motor deficits, increased sociability and anxiety. Unexpectedly, 70% of the genes with significantly decreased mRNA levels in the mutant mouse cortex are involved in myelination, and mutant mice had reduced mature oligodendrocyte cell numbers, reduced myelin thickness and impaired axonal conductivity. Restoring myelination properties with clemastine or increasing axonal conductivity rescued the behavioural deficits. Frontal cortex from WS patients similarly showed reduced myelin thickness, mature oligodendrocyte cell numbers and mRNA levels of myelination-related genes. Our study provides molecular and cellular evidence for myelination deficits in WS linked to neuronal deletion of Gtf2i.
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| Overall design |
Frontal cortex (BA9) human tissue samples.
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| Contributor(s) |
Barak B, Feng G |
| Citation missing |
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| |
| Submission date |
Mar 25, 2019 |
| Last update date |
Apr 02, 2020 |
| Contact name |
Boaz Barak |
| E-mail(s) |
barakboaz@gmail.com
|
| Organization name |
Tel Aviv University
|
| Street address |
122 Sharett Bldg
|
| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE128841 |
Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioural and myelin alterations rescuable by a remyelinating drug |
|
| Relations |
| BioProject |
PRJNA529023 |
| SRA |
SRP189418 |
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