Morphological characterization of the Alpha A- and Alpha B-crystallin double knockout mouse lens

One approach to resolving some of the in vivo functions of alpha-crystallin is to generate animal models where one or both of the alpha-crystallin gene products have been eliminated. In the single alpha-crystallin knockout mice, the remaining alpha-crystallin may fully or partially compensate for some of the functions of the missing protein, especially in the lens, where both alpha A and alpha B are normally expressed at high levels. The purpose of this study was to characterize gross lenticular morphology in normal mice and mice with the targeted disruption of alpha A- and alpha B-crystallin genes (alpha A/BKO). Lenses from 129SvEvTac mice and alpha A/BKO mice were examined by standard scanning electron microscopy and confocal microscopy methodologies. Equatorial and axial (sagittal) dimensions of lenses for alpha A/BKO mice were significantly smaller than age-matched wild type lenses. No posterior sutures or fiber cells extending to the posterior capsule of the lens were found in alpha A/BKO lenses. Ectopical nucleic acid staining was observed in the posterior subcapsular region of 5 wk and anterior subcapsular cortex of 54 wk alpha A/BKO lenses. Gross morphological differences were also observed in the equatorial/bow, posterior and anterior regions of lenses from alpha A/BKO mice as compared to wild mice. These results indicated that both alpha A- and alpha B-crystallin are necessary for proper fiber cell formation, and that the absence of alpha-crystallin can lead to cataract formation.