基于mSOD1转基因小鼠模型对肌萎缩侧索硬化症特征蛋白的鉴定及验证OA

Objective To identify and validate the characteristic proteins in the development progres-sion of amyotrophic lateral sclerosis(ALS)based on the mutant superoxide dismutase 1(mSOD1)transgenic mouse model.Methods The mSOD1 transgenic mouse model was constructed,and the proteomics was used to detect the protein expression profile differences in the brain tissues and muscle tissues between the ALS group and wild-type mice(WT group).The enrichment analysis,WGCNA analysis and PPI network construc-tion were conducted.RT-qPCR,Western blot and immunohistochemistry were used to conduct the verifica-tion.Results The mSOD1 transgenic mouse ALS model was successfully established.The differential analysis showed that there was significantly difference in protein expression in the brain and muscle tissues between the MLS group and Wt group.WGCNA showed that the Turquoise protein module was associated with ALS occurrence,and the PPI analysis results showed that chaperonin containing TCP1-subunit 2(CCT2),recombi-nant human phospho-stress-inducible protein 1(STIP1)and heat shock protein 70kDa protein 1A(HSPA1A)might be the characteristic proteins in ALS development process.The RT-qPCR results showed that CCT2,STIP1 and HSPA1A in the ALS group were higher than those in the WT group,and the difference was statis-tically significant(P<0.05).Conclusion CCT2,STIP1 and HSPA1A may be the characteristic proteins in the developing process of ALS caused by mSOD1 mutation.