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