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Cataract-causing allele in CRYAA (Y118D) proceeds through endoplasmic reticulum stress in mouse model.
Jia, Zhe-Kun; Fu, Chen-Xi; Wang, Ai-Ling; Yao, Ke; Chen, Xiang-Jun.
Afiliación
  • Jia ZK; Eye Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Fu CX; Eye Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Wang AL; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310020, China.
  • Yao K; Eye Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China. E-mail:xlren@zju.du.cn.
  • Chen XJ; Eye Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Zool Res ; 42(3): 300-309, 2021 May 18.
Article en En | MEDLINE | ID: mdl-33929105
As small heat shock proteins, α-crystallins function as molecular chaperones and inhibit the misfolding and aggregation of ß/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 CRYAA-Y118D 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Catarata / Cadena A de alfa-Cristalina / Modelos Animales de Enfermedad / Estrés del Retículo Endoplásmico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Zool Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Catarata / Cadena A de alfa-Cristalina / Modelos Animales de Enfermedad / Estrés del Retículo Endoplásmico Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Zool Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: China