Cataract-causing allele in CRYAA(Y118D)proceeds through endoplasmic reticulum stress in mouse model  

作　　者：Zhe-Kun Jia Chen-Xi Fu Ai-Ling Wang Ke Yao Xiang-Jun Chen 

机构地区：[1]Eye Center of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310009,China [2]Institute of Translational Medicine,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310020,China

出　　处：《Zoological Research》2021年第3期300-309,共10页动物学研究（英文）

基　　金：This study was supported by the National Natural Science Foundation of China(31872724,81900837,81870641,82070939);Zhejiang Province Key Research and Development Program(2019C03091,2020C03035)。

摘　　要：As small heat shock proteins,α-crystallins function as molecular chaperones and inhibit the misfolding and aggregation ofβ/γ-crystallins.Genetic mutations of CRYAA are associated with protein aggregation and cataract occurrence.One possible process underlying cataract formation is that endoplasmic reticulum stress(ERS)induces the unfolded protein response(UPR),leading to apoptosis.However,the pathogenic mechanism related to this remains unexplored.Here,we successfully constructed a cataract-causing CRYAA(Y118D)mutant mouse model,in which the lenses of the CRYAA-Y118D mutant mice showed severe posterior rupture,abnormal morphological changes,and aberrant arrangement of crystallin fibers.Histological analysis was consistent with the clinical pathological characteristics.We also explored the pathogenic factors involved in cataract development through transcriptome analysis.In addition,based on key pathway analysis,up-regulated genes in CRYAAY118D mutant mice were implicated in the ERS-UPR pathway.This study showed that prolonged activation of the UPR pathway and severe stress response can cause proteotoxic and ERS-induced cell death in CRYAA-Y118D mutant mice.

关 键 词：CATARACT αA-crystallin Unfolded protein response Endoplasmic reticulum stress 

分 类 号：R776.1[医药卫生—眼科]