The Cryab-R120G knock-in mouse was developed to study a human hereditary myopathy and cataracts. Normally functioning as a chaperone, the mutated form of αB-crystallin (Cryab-R120G) has been shown to form amyloid β-sheet structures in vitro. We have previously shown that age-related cataracts in human lens tissue contain amyloid β-sheet structures that are related to the disease pathology of scattering light. We used two-dimensional infrared (2DIR) spectroscopy to compare the aggregated proteins in the Cryab-R120G knock-in mouse model to human lenses in order to determine the protein structural relevance of the Cryab-R210G model to general age-related cataract disease. Using the spectral signatures of diagonal peak ratio, cross peak location and intensity, and anharmonic shift, we evaluated the protein secondary structures present in the mutant mouse tissue as compared to wild type mice lenses and human lenses with and without cataract. We estimated that the lenses contained fewer amyloid structures than lenses with diagnosed cataract but propose that they may serve as a good model for drug development studies targeting lenses with some amyloid, before cataract diagnosis and surgery is needed.

2DIR imaging of amyloid β-sheets in the Cryab-R120G knock-in mouse model

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.