Wdr13-/0 compared to wild-type mice hippocampus and pre-frontal cortex iTRAQ proteomics

ABSTRACT: Wdr13 has been implicated in memory and mental disorders, particularly in X-linked intellectual disability (XLID) in animal studies and in humans. The exact molecular function of Wdr13 is still largely unknown. In order to find out the role of Wdr13 in brain, we chose to characterize Wdr13 gene knockout mice and dissect the molecular mechanisms behind its action. We found that Wdr13 expresses majorly in hippocampal formation, cerebral cortex, cerebellum and striatum. Wdr13-/0 mice show mild anxiety but fared better than the wild type mice in memory tests. This phenotype was found to be correlated with increase in level of synaptic genes like Syn1, Camk2a, Sv2b and voltage gated ion channels. Interestingly, exposure to three/four weeks of social isolation caused symptoms of major depressive disorder in the Wdr13-/0 mice which was associated with loss in dendritic branches in hippocampal CA1 neurons and significant decrease in synaptic genes like Syn1, Rab3a, Nrxn2. We found GATA1, a common negative Transcription Factor for the above-mentioned and also a marker of MDD (Major Depressive Disorder) to be upregulated in the Wdr13-/0 mice after social isolation. WDR13 overexpression caused decrease in GATA1 expression in IMR32- human neuroblastoma cell line indicating a possible regulation of GATA1 by WDR13. Wdr13 thus becomes an important candidate gene to be involved in Major Depression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Shiladitya Mitra  

LAB HEAD: Suman Thakur

PROVIDER: PXD002466 | Pride | 2017-01-03

REPOSITORIES: Pride