Abstract
Purpose: :
Alpha-catenin is a cytoplasmic protein that participates in cell-cell adhesion via interactions with beta-catenin and cadherins. We have examined the role of alpha-catenin-mediated adhesion in lens and retinal development in mouse eyes lacking expression of alpha-E-catenin.
Methods: :
Mice were generated by crossing nestin-cre and alpha-E-catenin-lox P mice. Eyes were taken at P1, P12 and P28, fixed, cryosectioned and Nissl stained, immunolabeled or TUNEL stained. Control mice were processed in parallel for comparison.
Results: :
Previous studies have shown that nestin is expressed in lens epithelium, lens fiber cells and neural retina in embryonic mice. Conditional knockout of alpha-catenin, by nestin-cre leads to degeneration of the lens and anterior chamber structures. P28 animals exhibit microphthalmia and hyperpigmentation, with the entire cornea lined with pigmented cells. The lens and ciliary body are hypotrophic. At P12 and P28, most of the lens is absent. At P1, TUNEL staining reveals massive cell death in the central and posterior lens suggesting loss of lens fiber cells, while few dying cells are noted in controls. The outer nuclear layer contains photoreceptor rosettes at P12 and P28, with some rosettes extending into the inner retinal layers. Photoreceptors express recoverin and rhodopsin as in controls, but the distribution of rhodopsin is altered. At P12 and P28, cell death measured by TUNEL labeling in the neural retina is elevated compared to controls. Inner retinal lamination appears normal and immunolabeling confirms the presence of the major retinal cell classes.
Keywords: development • cell adhesions/cell junctions • apoptosis/cell death