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

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