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| Status |
Public on Jan 05, 2018 |
| Title |
Abnormal microglia and enhanced inflammation-related gene transcription in mice with conditional deletion of Ctcf in Camk2a-Cre-expressing neurons [Whole_HC_CTCF] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying 3D chromatin structure. Human mutations in CTCF cause intellectual disability and autistic features. Knocking out Ctcf in mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked out Ctcf postnatally in glutamatergic forebrain neurons under the control of Camk2a-Cre. Ctcf loxP/loxP;Camk2a-Cre (Ctcf CKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor coordination, and decreased sociability by 4 months of age. Ctcf CKO mice also had reduced dendritic spine density in the hippocampus and cerebral cortex. Microarray analysis of mRNA from Ctcf CKO mouse hippocampus identified increased transcription of inflammation-related genes linked to microglia. Separate microarray analysis of mRNA isolated specifically from Ctcf CKO mouse hippocampal neurons by ribosomal affinity purification identified upregulation of chemokine signaling genes, suggesting crosstalk between neurons and microglia in Ctcf CKO hippocampus. Finally, we found that microglia in Ctcf CKO mouse hippocampus had abnormal morphology by Sholl analysis and increased immunostaining for CD68, a marker of microglial activation. Our findings confirm that Ctcf KO in postnatal neurons causes a neurobehavioral phenotype in mice and provide novel evidence that CTCF depletion leads to overexpression of inflammation-related genes and microglial dysfunction.
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| Overall design |
To compare whole hippocampus gene expression in Ctcf loxP/loxP (control) and Ctcf loxP/loxP; Camk2a-Cre (Ctcf CKO) mice.
3 pooled samples of each genotype were prepared by collecting total RNA from the hippocampal tissue of 3 adult (3-6 months old) mice of both sexes.
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| Contributor(s) |
Barve RA, McGill BE |
| Citation(s) |
29133437 |
| Submission date |
Jan 05, 2018 |
| Last update date |
Mar 01, 2018 |
| Contact name |
Ruteja A Barve |
| Organization name |
Washington University
|
| Department |
Genetics
|
| Street address |
4515 McKinley Ave
|
| City |
St.Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL10333 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Feature Number version) |
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| Samples (8)
|
| GSM2913850 |
Hippocampus_WT_BiologicalReplicate1_TechnicalReplicate1 |
| GSM2913851 |
Hippocampus_WT_BiologicalReplicate2_TechnicalReplicate1 |
| GSM2913852 |
Hippocampus_WT_BiologicalReplicate3_TechnicalReplicate1 |
| GSM2913853 |
Hippocampus_WT_BiologicalReplicate1_TechnicalReplicate2 |
| GSM2913854 |
Hippocampus_CKO_BiologicalReplicate1_TechnicalReplicate1 |
| GSM2913855 |
Hippocampus_CKO_BiologicalReplicate2_TechnicalReplicate1 |
| GSM2913856 |
Hippocampus_CKO_BiologicalReplicate3_TechnicalReplicate1 |
| GSM2913857 |
Hippocampus_CKO_BiologicalReplicate1_TechnicalReplicate2 |
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| This SubSeries is part of SuperSeries: |
| GSE108827 |
Abnormal microglia and enhanced inflammation-related gene transcription in mice with conditional deletion of Ctcf in Camk2a-Cre-expressing neurons |
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| Relations |
| BioProject |
PRJNA428748 |
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