Murine Adult Cortex: Gtf2i (+/Δex2 ) VS WT (+/+)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE41251 | GEO | 2014/10/20
SECONDARY ACCESSION(S): PRJNA176338
REPOSITORIES: GEO
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Project description:Transcriptional profiling of mouse cortex tissue comparing control animals with Gtf2i-mutated mouse (Gtf2i+/Δex2 ). Goal was to determine the specific deregulated genes in the cortex of mutated animals. Pools of total RNA derived from five-three mice of each genotype were subjected to microarray analysis. We compared pools instead of single individuals in order to minimize individual and technically-related variation. The original raw data file (i.e. Agilent feature extraction files) are not available. The modified raw data files are provided along with the file contents description (raw_data_readme.txt available on Series records).
2014-10-20 | E-GEOD-41251 | biostudies-arrayexpress
Project description:Data present the expression analysis of different mouse ES cell line with altered expression of GTF2I. We used microarrays to detail the global programme of gene expression underlying altered expression of GTF2I and identified distinct classes of deregulated genes
2013-07-12 | E-GEOD-48790 | biostudies-arrayexpress
Project description:Data present the expression analysis of different mouse ES cell line with altered expression of GTF2I.
2013-07-12 | GSE48790 | GEO
Project 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.
2019-03-26 | GSE128840 | GEO
Project 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.
2019-03-26 | GSE128839 | GEO
Project 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.
2019-03-26 | GSE128838 | GEO
Project description:Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion leads to Williams-Beuren syndrome (WBS), while duplication causes 7q11.23 microduplication syndrome (7Dup). Converging evidence indicates GTF2I, from the 7q11.23 locus, is a key mediator of the cognitive-behavioral phenotypes associated with WBS and 7Dup. Here we integrate molecular profiling of patient-derived cortical organoids (COs) and transgenic mouse models to dissect 7q11.23 disease mechanisms. Proteomic and transcriptomic profiling of COs revealed opposite dynamics of neural progenitor proliferation and transcriptional imbalances, leading to precocious excitatory neuron production in 7Dup. The accelerated excitatory neuron production in 7Dup COs could be rescued by GTF2I knockdown. Transgenic mice with Gtf2i duplication recapitulated early neuronal differentiation defects and ASD-like behaviors. Remarkably, inhibition of LSD1, a downstream effector of GTF2I, was sufficient to rescue ASD-like phenotypes. We propose that the GTF2I-LSD1 axis constitutes a molecular pathway amenable to therapeutic intervention.
2024-01-26 | PXD036770 | Pride
Project description:In order to identify the effects of the induction of the gene of interest (GTF2I) on the mouse ES transcriptome, we performed Affymetrix Gene-Chip hybridization experiments for the inducible not-tagged cell line Transcriptome analysis of the inducible transgenic mouse ES cell line overexpressing the human isorofm of the gene GTF2I
2019-10-11 | GSE95270 | GEO
Project description:We previously identified a recurrent mutation L424H in the transcription factor GTF2I in thymic epithelial tumors. The precise role of the GTF2I mutation in these tumors is unclear. Here we describe the generation and characterization of a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. The Gtf2i mutation impairs development of thymic medulla and maturation of medullary thymic epithelial cells in the young mice and causes tumor formation in the thymus of the aged KI mice. To characterize the molecular features of murine thymomas, we performed digital spatial profiling with GeoMx moue whole transcriptome atlas assay with FFPE thymic tissues of 4 KI and 4 control mice.
2023-01-25 | GSE200784 | GEO
Project description:Williams syndrome is a neurodevelopmental disorder caused by a 1.5-1.8Mbp deletion on chromosome 7q11.23, affecting the copy number of 26-28 genes. Phenotypes of Williams syndrome include cardiovascular problems, craniofacial dysmorphology, deficits in visual spatial cognition, and a characteristic hypersocial personality. There are still no genes in the region that have been consistently linked to the cognitive and behavioral phenotypes, although human studies and mouse models have led to the current hypothesis that the general transcription factor 2 I family of genes, GTF2I and GTF2IRD1, are responsible. Here we test the hypothesis that these two transcription factors are sufficient to reproduce the phenotypes that are caused by deletion of the Williams syndrome critical region (WSCR). We compare a new mouse model with loss of function mutations in both Gtf2i and Gtf2ird1 to an established mouse model lacking the complete WSCR. We show that the complete deletion model has deficits across several behavioral domains including social communication, motor functioning, and conditioned fear that are not explained by loss of function mutations in Gtf2i and Gtf2ird1. Furthermore, transcriptome profiling of the hippocampus shows changes in synaptic genes in the complete deletion model that are not seen in the double mutants. Thus, we have thoroughly defined a set of molecular and behavioral consequences of complete WSCR deletion, and shown that other genes or combinations of genes are necessary to produce these phenotypic effects.
2020-01-11 | GSE127723 | GEO