PXD009692

PXD009692 is an original dataset announced via ProteomeXchange.

Title	Neuroproteomics in Brd1 knockout mice (hippocampus - synaptosome)
Description	Genetic and molecular studies have implicated the bromodomain containing 1 (BRD1) gene in the pathogenesis of schizophrenia and bipolar disorder. Accordingly, mice heterozygous for a targeted deletion of Brd1 (Brd1+/- mice) show behavioural phenotypes with broad translational relevance to psychiatric disorders. BRD1 encodes a scaffold protein that affects the expression of many genes through modulation of histone acetylation. BRD1 target genes have been identified in cell lines; however the impact of reduced Brd1 levels on the brain proteome is largely unknown. In this study, we applied label-based quantitative mass spectrometry to profile the frontal cortex, hippocampus and striatum proteome and synaptosomal proteome of female Brd1+/- mice. We successfully quantified between 1537 and 2196 proteins and show widespread changes in protein abundancies. By integrative analysis of human genetic data, we find that the differentially abundant proteins in frontal cortex are enriched for schizophrenia risk further linking the actions of BRD1 to psychiatric disorders. Affected proteins were further enriched for proteins involved in processes known to influence neuronal and dendritic spine morphology e.g. regulation of actin cytoskeleton dynamics and mitochondrial function. Directly prompted in these findings, we investigated dendritic spine morphology of pyramidal neurons in anterior cingulate cortex and found them significantly altered, including reduced size of small dendritic spines and decreased number of the mature mushroom type. Collectively, our study describes known as well as new mechanisms related to BRD1 dysfunction and its role in psychiatric disorders, and provides evidence for the molecular and cellular dysfunctions underlying altered neurosignalling and cognition in Brd1+/- mice.
HostingRepository	PRIDE
AnnounceDate	2019-01-07
AnnouncementXML	Submission_2019-01-07_02:43:23.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Veerle Paternoster
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-07 04:56:07	ID requested
⏵ 1	2019-01-07 02:43:25	announced

Paternoster V, Svanborg M, Edhager AV, Rajkumar AP, Eickhardt EA, Pallesen J, Grove J, Qvist P, Fryland T, Wegener G, Nyengaard JR, Mors O, Palmfeldt J, B, ø, rglum AD, Christensen JH, mice unmask dendritic spine pathology and show enrichment for schizophrenia risk. Neurobiol Dis, 124():479-488(2019) [pubmed]

curator keyword: Biological

submitter keyword: BRD1, mouse, frontal cortex, cell lysate, TMT, LC-MS/MSBRD1, mouse,hippocampus, synaptosome, TMT, LC-MS/MS

Johan Palmfeldt
contact affiliation	Research Unit for Molecular Medicine, Department of clinical Medicine, Aarhus University, Aarhus, Denmark
contact email	johan.palmfeldt@clin.au.dk
lab head
Veerle Paternoster
contact affiliation	Aarhus University, Denmark
contact email	veerle@biomed.au.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009692
     1. Label: PRIDE project
     2. Name: Neuroproteomics in Brd1 knockout mice (hippocampus - synaptosome)