Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription profiling of mouse SAP102 and PSD-95 knockouts compared to their wild-type littermates

ABSTRACT: Effect of ablation of SAP102 or PSD-95 genes in mice compared to wild-types littermates

ORGANISM(S): Mus musculus

SUBMITTER: Luis Valor

PROVIDER: E-MEXP-1159 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Clustered gene expression changes flank targeted gene loci in knockout mice.

Valor Luis M LM Grant Seth G N SG

PloS one 20071212 12

<h4>Background</h4>Gene expression profiling using microarrays is a powerful technology widely used to study regulatory networks. Profiling of mRNA levels in mutant organisms has the potential to identify genes regulated by the mutated protein.<h4>Methodology/principle findings</h4>Using tissues from multiple lines of knockout mice we have examined genome-wide changes in gene expression. We report that a significant proportion of changed genes were found near the targeted gene.<h4>Conclusions/si ...[more]

PMID: 18074027

Similar Datasets

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment [2]

Project description:Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we utilize UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding for proteins known to interact with postsynaptic AMPA and NMDA receptors. Loci in/near Discs Large Homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P<5x10-8) for BF% and/or BMI. To further evaluate the functional role of PSD-95 (gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PDZ-domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising new therapeutic avenue for sustained weight loss.

2024-01-04 | GSE251836 | GEO

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment

Project description:Abstract: Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we utilize UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding for proteins known to interact with postsynaptic AMPA and NMDA receptors. Loci in/near Discs Large MAGUK Scaffold Protein 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P<5x10-8) for BF% and/or BMI. To further evaluate the functional role of PSD-95 (gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PDZ-domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising new therapeutic avenue for sustained weight loss.

2024-03-11 | GSE221549 | GEO

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment

2024-06-16 | PXD047515 | Pride

PSD-95 interactome in presence and absence of Xph20 intrabody

Project description:In the context of intrabodies development for the synaptic protein PSD-95, we use proteomic approaches to evaluate the possible impact of one of our evolved PSD-95 binders on the endogenous PSD-95 function. More precisely, we compare the interactome of PSD-95 in presence or absence of the Xph20 binder in primary rat neuron culture infected with the Xph20-derived probe or a control protein, EGFP.

2024-01-26 | PXD045002 | Pride

Transcription profiling time series of mouse hippocampal neuronal cultures during development

Project description:The expression of components of the synapse proteome was examined in genome-wide transcriptome profiles of differentiating hippocampus neurons (from 0.25 to 16 days in vitro) and microelectrode arrays was used to correlate the gene expression with electrical activity.

2007-02-26 | E-MEXP-878 | biostudies-arrayexpress

MS analysis of cellular targets of an engineered selective PSD-95 PDZ domain ligand

Project description:Designing highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces and PPI domains. We report here a strategy that addresses this challenge by using a semi-rational approach that separates the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by employing a selection by phage display coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to bind against the target interface. We have applied this approach to PSD-95, an essential multi-PDZ domain-containing synaptic scaffold protein that belongs to a larger family of paralogs. We show here that with this strategy we could specifically target a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides the first paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules. This archive contains the comparative LC/MS/MS analysis of cellular targets of an engineered selective PSD-95 PDZ domain ligand, Xph20-ETWV, against the fusion with a naïve clone, Xph0-ETWV and a control non-binding protein (mSacrlet-i).

2019-11-12 | PXD015313 | Pride

Transcription profiling of Pseudomonas aeruginosa overexpressing the ECF sigmas PA0149, PA2050, PA2093 and PA4896 involved in cell-surface signaling systems

Project description:Cell-surface signaling is a sophisticated regulatory mechanism used by gram-negative bacteria to sense signals from outside the cell and transmit them into the cytoplasm. This regulatory system consists of an outer membrane-localized TonB-dependent receptor (TonB-dependent transducer), a cytoplasmic membrane-localized anti-sigma factor and an extracytoplasmic function (ECF) sigma factor. By microarray analysis we have identified the regulons of four novel P. aeruginosa signaling systems. For that, the ECF sigmas PA0149, PA2050, PA2093 and PA4896 have been overexpressed in P. aeruginosa and their target gene candidates have been identified using DNA microarray. Experiment Overall Design: Five different samples are analyzed namely P. aeruginosa (pMMB67EH) (control/reference sample), P. aeruginosa (pMMB-PA4896) (overexpressing the PA4896 ECF sigma factor), P. aeruginosa (pMMB-PA0149) (overexpressing the PA0149 ECF sigma factor), P. aeruginosa (pMMB-PA2050) (overexpressing the PA2050 ECF sigma factor), and P. aeruginosa (pMMB-PA2093) (overexpressing the PA2093 ECF sigma factor). Two different replicates are included for the three first samples and one for the two last samples.

2008-06-16 | E-GEOD-9657 | biostudies-arrayexpress

PSD-95 IP

Project description:FUS is an RNA binding protein related to ALS/FTLD. Our aim is to elucidate the influence of FUS toward PSD-95 intractome.

2017-08-21 | PXD007522 | JPOST Repository

Transcription profiling of mouse heterozygous periphilin knockouts compared to wt littermates

Project description:Periphilin is a protein which is involved in multiple processes in vivo, including terminal differentiation of keratinozytes as well as cell-cycle and cancer related functions. Here we generated mice with a targeted disruption of the periphilin-1 gene to explore its physiological role from an organismic perspective. In accordance with a ubiquitous expression of periphilin in the murine embryo, the homozygous deficiency of periphilin is lethal in early embryogenesis. We therefore characterized mice with a disruption of only one periphilin allele. As heterozygous periphilin knockout mice show no obvious histological alterations and have no apparent behavioural phenotypes, we compared whole transcriptome RNA expression profiles of total brain tissue of periphilin+/- knockout mice and wild type littermates for an in-depth analysis of heterozygous animals. In periphilin+/- knockout mice, 3 probe sets were indicative of significant differential expression (p â¤ 0.05, SLR â¥ 1 which is equivalent to 2 fold). Two of these probe sets (1438864_at and 1439170_at) refer to unannotated or unclassifiable genes. According to the NetAffxâ¢ Analysis Center, the third probe set (1447831_s_at) is assigned to myotubularin related protein 7 (Mtmr7). The probe set, however, lies upstream of the Mtmr7 gene (Ensembl gene ENSMUSG00000039431), and its signal is therefore not representative for the Mtmr7 gene. Quantitative RT-PCR (qRT-PCR) analysis with a primer set specific for Mtmr7 confirmed that its expression is not altered in periphilin+/- knockout mice (relative expression compared to wild type: 0.924; p = 0.419). In summary, none of more than 45.000 covered transcripts is differentially expressed in periphilin+/- knockout mice in comparison to wild type littermates. Experiment Overall Design: Whole brains of three male 2-months-old periphilin+/-knockout mice and three C57BL/6-wild type littermates

2009-04-12 | E-GEOD-14059 | biostudies-arrayexpress

MS analysis of photocrosslink adducts for the mapping of interaction sites of selective engineered PSD-95 PDZ domain ligands

Project description:Designing highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces and PPI domains. We report here a strategy that addresses this challenge by using a semi-rational approach that separates the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by employing a selection by phage display coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to bind against the target interface. We have applied this approach to PSD-95, an essential multi-PDZ domain-containing synaptic scaffold protein that belongs to a larger family of paralogs. We show here that with this strategy we could specifically target a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides the first paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules. This archive contains the mapping by photocrosslinking and LC/MS/MS analysis of the interaction sites of engineered selective PSD-95 PDZ domain ligands, Xph20-ETWV, Xph20-Stg and Xph20-ETMA.

2019-11-12 | PXD015366 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data