Whole Genome Bisulfite Sequencing Study on Parkinson′s Disease Model Mice Genetically Modified by A53T Mutant α-Synuclein in Midbrain
- VernacularTitle:转突变型A53Tα-突触核蛋白基因的帕金森模型小鼠中脑的全基因组甲基化测序分析
- Author:
Ting WU
1
;
Lin LIU
1
;
Zhao LI
1
;
Xian LIN
1
Author Information
1. Guangdong Province Key Laboratory of Brain Function and Disease，Zhongshan School of Medicine，Sun Yat-sun University，Guangzhou 510080，China
- Publication Type:Journal Article
- Keywords:
Parkinson′s , disease, α-synuclein, methylation, whole genome
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(1):53-59
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】To investigate the effect of PD-related gene SNCA mutated in A53T on methylation modification in the dopaminergic neurons from the mouse midbrain.【Methods】The midbrain tissue from the A53T mutant human α-synuclein（hA53T α-syn）transgenic mice and non-transgenic（nTg）mice were isolated α-synmice. Bisulfite-sequencing（BS-seq）was utilized for analyzing the DNA methylation of 12-month-old of hA53T α-synmice and nTg mice at a whole genome level. Subsequently，differentially methylated regions（DMRs）were screened for GO enrichment analyses.【Results】Through comparative analyses，481 DMRs were found. Among the data ，hypermethylated and hypomethylated DMRs accounted for 257 and 224 respectively. These DMRs involved in ubiquitin degradation pathway-related genes， including Ubqln2，HECTD4，Rnf157 genes；serine/threonine protein kinase PINK1 gene，etc. Enrichment data revealed that the genes containing DMRs projected to 545 GO sub-terms，and significantly enriched in anatomical structure development，dendrite development，nervous system development，neuronal projection，etc.【Conclusion】The A53T mutation of SNCA gene which is related to PD could introduce DNA methylation alterations in mouse midbrain.
