Quantitative Proteomics Profile The Function Of WDR45 In Mouse Brain Regions

SENDA(static encephalopathy of childhood with neurodegeneration in adulthood)is a subtype of NBIA(Neurodegeneration with brain iron accumulation).The mutation of WDR45 gene at Xp11.23 was found in SENDA patients by exon sequencing.The major symptom of this disease is mental retardation in childhood,but the motor function develop normally.During adulthood the patient develop dementia and Parkinsonism.Iron accumulation in globus and substantia nigra was identified by NMR.In this study,we used the CRISPAR-Cas9 technique to construct WDR45 knockout mice to simulate the complex process of this disease.Behavioral experiments showed that WDR45 KO mice also displayed cognitive impairments,and Nissl staining confirmed that the nigra neurons were damaged.We performed proteomic analysis of three brain regions of the mouse,the prefrontal cortex,midbrain and the hippocampus,using tandem mass tag(TMT)-based quantitative mass spectrometry.Applying bioinformatic analysis of the differentially expressed proteins we discovered that most of the proteins were involved in lipid metabolism and endoplasmic reticulum synthesis and degradation.On the other hand,the interaction protein of WDR45 directly affects its related signal pathway.In this study,we construct WDR45 stable cell line and IP-MS to confirm the interaction protein group.