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 Zhe-Kun Jia;Chen-Xi Fu;Ai-Ling Wang;Ke Yao;Xiang-Jun Chen

作者机构：Eye Center of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Institute of Translational MedicineZhejiang University School of MedicineHangzhouZhejiang 310020China 

出 版 物：《Zoological Research》 (动物学研究（英文）)

年 卷 期：2021年第42卷第3期

页      面：300-309页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

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) 

主　　题：Cataract αA-crystallin Unfolded protein response Endoplasmic reticulum stress 

摘      要：As small heat shock proteins,α-crystallins function as molecular chaperones and inhibit the misfolding and aggregation ofβ/γ-*** mutations of CRYAA are associated with protein aggregation and cataract *** possible process underlying cataract formation is that endoplasmic reticulum stress(ERS)induces the unfolded protein response(UPR),leading to ***,the pathogenic mechanism related to this remains ***,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 *** analysis was consistent with the clinical pathological *** also explored the pathogenic factors involved in cataract development through transcriptome *** addition,based on key pathway analysis,up-regulated genes in CRYAAY118D mutant mice were implicated in the ERS-UPR *** 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.