Wdr13 knockout mice develops MD like phenotype on chronic stress

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Shiladitya Mitra  

LAB HEAD: Suman Thakur

PROVIDER: PXD004545 | Pride | 2018-05-28

REPOSITORIES: Pride