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Neuronal deletion of Gtf2i, associated with Williams syndrome, causes behavioural and myelin alterations rescuable by a remyelinating drug [human]

gse128840

Description

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.

Overall Design

Frontal cortex (BA9) human tissue samples.

Histogram

Data and Resources

Additional Info

Field Value
Source https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE128840
Type of Data

Expression profiling by high throughput sequencing

Technology

RNA Sequencing

GSE Submission Date 25/03/2019
GSE Authors Boaz,,Barak; Guoping Feng
Dataset Last Updated December 1, 2020, 18:54 (UTC)
Dataset Created December 1, 2020, 17:09 (UTC)