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| Status |
Public on Jan 16, 2020 |
| Title |
Tet3 ablation in adult brain neurons increases anxiety-like behavior and regulates cognitive function in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
TET3 is a member of the Ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is absent in astrocytes. To investigate the function of TET3 in adult post-mitotic neurons, we crossed Tet3 floxed mice with a neuronal Cre-expressing mouse line, Camk2a-CreERT2, obtaining a Tet3 conditional KO mouse line. Ablation of Tet3 in adult mature neurons resulted in increased anxiety-like behavior with concomitant hypercorticalism, and impaired hippocampal-dependent spatial orientation. Transcriptome and gene-specific expression analysis of the hippocampus showed dysregulation of genes involved in glucocorticoid signaling pathway (HPA axis) in the ventral hippocampus, whereas upregulation of immediate early genes (IEGs) was observed in both dorsal and ventral hippocampal areas. Additionally, Tet3 cKO mice exhibit increased dendritic spine maturation in the ventral CA1 hippocampal subregion. Based on these observations, we suggest that TET3 is involved in molecular alterations, that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of psychiatric disorders.
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| Overall design |
Tet3 fl/fl mice on a C57BL/6N background were crossed with B6;129S6 mice (24 JAX stock #012362 – Camk2a-CreERT2) expressing a tamoxifen-inducible Cre recombinase under the control of the mouse Camk2a promoter region to generate mice heterozygous for the floxed Tet3 allele and Cre- recombinase. These mice were interbred with C57BL/6N mice homozygous for the floxed Tet3 allele to generate mice heterozygous for Cre-recombinase and homozygous for the floxed Tet3 allele, designated as Tet3 cKO mice. Mice homozygous for the Tet3 floxed allele, but not carrying Cre-recombinase, were used as controls. From both groups, dorsal and ventral hippocampal brain regions were macrodissected and the RNA extracted. RNA-seq libraries were generated as described below.
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| Contributor(s) |
Antunes C, Da Silva JD, Guerra-Gomes S, Alves ND, Ferreira F, Loureiro-Campos E, Branco MR, Sousa N, Reik W, Pinto L, Marques C |
| Citation(s) |
32103150 |
| Submission date |
Nov 22, 2019 |
| Last update date |
Feb 28, 2020 |
| Contact name |
Miguel R Branco |
| E-mail(s) |
m.branco@qmul.ac.uk
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| Organization name |
Blizard Institute
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| Street address |
4 Newark Street
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| City |
London |
| ZIP/Postal code |
E1 2AT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA591161 |
| SRA |
SRP231437 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140850_controlVscKO_DorsalHipAllRunsGLM.differential_expression_edgeR.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
| GSE140850_controlVscKO_VentralHipAllRunsGLM.differential_expression_edgeR.txt.gz |
3.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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