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Transcriptomic profiling of a CamKII-Dars2 neuronal knockout mouse

ABSTRACT: Transcriptomic profiling of a CamKII-Dars2 neuronal knockout mouse

PROVIDER: PRJNA591892 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10534461_1.fastq.gz	Fastqsanger.gz
	SRR10534461_2.fastq.gz	Fastqsanger.gz
	SRR10534462_1.fastq.gz	Fastqsanger.gz
	SRR10534462_2.fastq.gz	Fastqsanger.gz
	SRR10534463_1.fastq.gz	Fastqsanger.gz

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Transcriptomic profiling of a CamKII-Dars2 neuronal knockout mouse

Project description:Purpose: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare, slowly progressive white matter disease caused by mutations in the mitochondrial aspartyl-tRNA synthetase (DARS2). While patients show characteristic MRI T2 signal abnormalities throughout the cerebral white matter, brain stem, and spinal cord, clinical symptoms appear quite variable and a multitude of gene variants have been associated with the disease. Here, Dars2 deletion from CamKIIα-expressing cortical and hippocampal neurons results in slowly progressive increases in behavioral activity at 5 months, and culminating by 9 months as severe brain atrophy, behavioral dysfunction, reduced corpus callosum thickness, and microglial morphology indicative of neuroinflammation. Methods: Cortical samples were collected from DARS2-Flox/CamKII-Cre(+) and DARS2-Flox/CamKII-Cre(-) at 14 weeks of age. RNA-seq libraries were prepared using purified RNA isolated from frozen tissue using the RNeasy Mini kit. RNA quality and concentration were assayed using a Fragment Analyzer instrument. RNA-seq libraries were prepared using the TruSeq Stranded mRNA PolyA (Unique Dual Index) kit.. Libraries were sequenced on an Illumina HiSeq 4000 instrument. Samples were taken from N=7 DARS2-Flox/CamKII-Cre(+) and N=6 DARS2-Flox/CamKII-Cre(-) male mice. Conclusions: RNA-seq based gene expression studies performed prior to the presentation of this severe phenotype reveal the upregulation of several pathways involved in immune activation, cytokine production and signaling, and the defense response regulation. Among these transcripts, Cystatin F (Cst7), a protease inhibitor recognized as a marker of neurodegenerative disease and active demyelination, is upregulated over 200-fold in mutant mice and may serve as a key regulator of disease progression.

2020-02-04 | GSE141055 | GEO

Identification of CaMKII-dependent H3S28p target genes

Project description:To identify direct CaMKII-dependent downstream genes of H3S28p we used chromatin-immunoprecipitation followed by massive parallel DNA sequencing (ChIPseq) analysis of isolated adult murine cardiomyocytes from CamKII WT as well as from CaMKIIγ/CaMKIIδ double knockout (DKO) . DKO and WT cells were subjected to long-term Iso treatment for 24 h to maximize CaMKII-dependent H3S28p.

2019-06-13 | E-MTAB-8011 | biostudies-arrayexpress

Gene expression microarray analysis on the dentate gyrus of alpha-CaMKII HKO mice

Project description:We previously found that mice with heterozygous knockout of the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha-CaMKII HKO mice) show various dysregulated behaviors, including cyclic variations in locomotor activity (LA), suggesting that alpha-CaMKII HKO mice may serve as an animal model showing infradian oscillation of mood. We performed gene expression microarray analysis of dentate gyrus from alpha-CaMKII HKO mice. Mice were selected for the sampling such that their LA levels varied among the mice.

2016-03-29 | GSE68293 | GEO

Gene expression microarray analysis on the dentate gyrus of alpha-CaMKII HKO mice

2016-03-29 | E-GEOD-68293 | biostudies-arrayexpress

Cpeb3 knockout cortical neuronal cultures

Project description:Cpeb3 knockout cortical neuronal cultures

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Proteome and phosphoproteome analysis of autophagy deficient ATG5flox:CamKII-Cre and ATG5flox:VGAT-Cre conditional knockout mice

Project description:The experiment was performed to find selective targets of autophagy in different subtypes of neurons. Therefore, brain tissue of conditional knockout mice lacking autophagy protein ATG5 in inhibitory or excitatory neurons was used. Cortices (ATG5flox:CamKII-Cre) / striata (ATG5flox:VGAT-Cre) of mice were mixed with lys6 labeled brain lysates as internal controls between the samples. Samples were measured by LC-MS/MS and resulting H/L ratios were used to quantify proteomic and phosphoproteomic changes.

2022-11-15 | PXD029435 | Pride

Identification of CaMKII splice variants expressed in the human hippocampus

Project description:Purpose: The goal of this study was to use deep sequencing to identify all splice variants of Calcium/calmodulin-dependent kinase II (CaMKII) expressed in the human hippocampus. Methods: Transcripts of CaMKII-encoding genes (CAMK2A, CAMK2B, CAMK2G, and CAMK2D) were sub-amplified by PCR from total RNA extracted from human hippocampal tissue samples from 3 donors. Illumina sequencing libraries were constructed by PCR from these initial pools of amplicons and sequenced on an Illumina MiSeq instrument. Sequencing reads passing quality controls were clustered on the basis of sequence identity or near-identity. Consensus sequences of clusters were mapped with known exons of CaMKII genes to identify the splice variant represented by each cluster. Donor 1 replicate 2, Donor 2, and Donor 3 libraries from genes CAMK2B, CAMK2G, and CAMK2D were first sequenced on a MiSeq Nano flow cell, then re-pooled for read balancing and sequenced again of a full-size MiSeq flow cell. For each library, reads from Nano and full-size flow cells were combined for subsequent analysis. Results: We perfomed the first comprehensive survey of CaMKII transcripts expressed in individual tissue samples (human hippocampus). We detected a total of 79 splice variants of the four human CaMKIIs: CaMKIIα (3), CaMKIIβ (30), CaMKIIγ (24), and CaMKIIδ (22), across tissue samples from 3 donors. This represents the vast majority of possible in-frame CaMKII splice variants (Sloutsky and Stratton, European Journal of Neuroscience, 2020; https://doi.org/10.1111/ejn.14761).

2020-07-21 | GSE154030 | GEO

Transcription profiling by array of hippocampi from wild type and alpha-CaMKII+/- mice

Project description:Comparison of the hippocampus of alpha-CaMKII+/- mice with control

2008-10-04 | E-MEXP-962 | biostudies-arrayexpress

Transcriptomic profiling of murine Nfe2l2 knockout melanoma cells

Project description:Transcriptomic profiling of murine Nfe2l2 knockout melanoma cells

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Metabolomic analysis of brain cortex from neuronal specific Depdc5 knockout in fed and fasting state

Project description:Caloric restriction and acute fasting are known to reduce seizures but through unclear mechanisms. In this study, we demonstrate that mTORC1 signaling is reduced after acute fasting of mice. In neurons, mTORC1 is most sensitive to withdrawal of leucine, arginine, and glutamine, which is dependent on DEPDC5. We performed metabolomic analysis of brain cortex from neuronal specific Depdc5 knockout in fed and fasting state. The Depdc5 neuronal specific knockout mice are resistant to sensing significant fluctuations in brain amino acid levels after fasting. These results establish that acute fasting reduces seizure susceptibility in a DEPDC5-dependent manner.

2022-07-27 | ST002237 | MetabolomicsWorkbench

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