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Series GSE140850 Query DataSets for GSE140850
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
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.
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.
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
Organization name Blizard Institute
Street address 4 Newark Street
City London
ZIP/Postal code E1 2AT
Country United Kingdom
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM4188879 dHip40-cKO
GSM4188880 dHip41-Control
GSM4188881 dHip43-cKO
BioProject PRJNA591161
SRA SRP231437

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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
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