Research article

Morphological characterization of the AlphaA- and AlphaB-crystallin double knockout mouse lens

Daniel L Boyle¹ , Larry Takemoto¹ , James P Brady² and Eric F Wawrousek³

¹  Kansas State University, Division of Biology, Ackert Hall, Manhattan, KS, USA

²  Ocular Gene Therapy, Genetic Therapy, Inc., 9 W Watikins Mill Rd, Gaithersburg, MD, USA

³  Lab of Molecular & Dev Biology, National Eye Institute, NIH, 6 Center Drive MSC 2730, Bethesda, MD, USA

author email corresponding author email

BMC Ophthalmology 2003, 3:3doi:10.1186/1471-2415-3-3

Published:	24 January 2003

Abstract

Background

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 alphaA and alphaB 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 alphaA- and alphaB-crystallin genes (alphaA/BKO).

Methods

Lenses from 129SvEvTac mice and alphaA/BKO mice were examined by standard scanning electron microscopy and confocal microscopy methodologies.

Results

Equatorial and axial (sagittal) dimensions of lenses for alphaA/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 alphaA/BKO lenses. Ectopical nucleic acid staining was observed in the posterior subcapsular region of 5 wk and anterior subcapsular cortex of 54 wk alphaA/BKO lenses. Gross morphological differences were also observed in the equatorial/bow, posterior and anterior regions of lenses from alphaA/BKO mice as compared to wild mice.

Conclusion

These results indicated that both alphaA- and alphaB-crystallin are necessary for proper fiber cell formation, and that the absence of alpha-crystallin can lead to cataract formation.