PXD004545-1

PXD004545 is an original dataset announced via ProteomeXchange.

Title	wdr13 knockout mice develops MD like phenotype on chronic stress
Description	WDR13 expresses from the X chromosome and has a highly conserved coding sequence. There have been multiple associations of WDR13 with memory and psychiatric disorders. However, its detailed function in context of brain and behavior remains unknown. We characterized the behavioral phenotype of male mice lacking the homologue of WDR13 gene (Wdr13-/0). Mice were evaluated for changes in anxiety, learning and memory, and chronic stress induced behavioral deficits. Taking cue from analysis of its expression in the brain, we chose hippocampus and pre-frontal cortex for molecular studies to delineate its function. In the absence of Wdr13, there was a significant upregulation of synaptic proteins, viz., SYN1, RAB3A, CAMK2A etc accompanied with better memory retention in mice. Interestingly, three weeks social isolation stress resulted in downregulation of aforementioned synaptic proteins, decreased exploration time in central area of Open field test, increased immobility in Forced swim test, and reduced dendritic arborations of hippocampal CA1 neurons- hallmarks of Major Depressive Disorder (MDD) in Wdr13-/0 mice. This phenotype could be rescued by short imipramine treatment. We hypothesise that one of the key factors behind the MDD like phenotype in these mice was upregulation of transcription factor GATA1. Parallel work from our lab has indicated WDR13 to interact with multiple nuclear receptors and acting majorly as a co-repressor. Absence of Wdr13 resulted in de-regulated expression of a number of genes including multiple synaptic genes leading to observed phenotypes. Summarily, our data provides functional evidence for the role of Wdr13 in memory retention and in withstanding chronic stress induced depression.
HostingRepository	PRIDE
AnnounceDate	2018-05-28
AnnouncementXML	Submission_2018-05-28_02:00:10.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shiladitya Mitra
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-07-11 02:51:11	ID requested
⏵ 1	2018-05-28 02:00:12	announced

Mitra S, Sameer Kumar GS, Jyothi Lakshmi B, Thakur S, Kumar S, Gene Predisposes Mice to Mild Social Isolation - Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins. Front Mol Neurosci, 11():133(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: mice, knockout, wdr13

Suman Thakur
contact affiliation	Centre for Cellular and Molecular Biology, Hyderabad, India
contact email	sst@ccmb.res.in
lab head
Shiladitya Mitra
contact affiliation	Centre for Cellular and Molecular Biology
contact email	shiladitya.mitra@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004545
     1. Label: PRIDE project
     2. Name: wdr13 knockout mice develops MD like phenotype on chronic stress