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Development ePress online publication date 26 Jan 2006
doi: 10.1242/dev.02262

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Research article

Caspase-dependent secondary lens fiber cell disintegration in {alpha}A-/{alpha}B-crystallin double-knockout mice


Viktor Morozov* and Eric F. Wawrousek
* Author for correspondence (e-mail: morozovv{at}nei.nih.gov)

{alpha}B-crystallin has been demonstrated, in tissue culture experiments, to be a caspase 3 inhibitor; however, no animal model studies have yet been described. Here, we show that morphological abnormalities in lens secondary fiber cells of {alpha}A-/{alpha}B-crystallin gene double knockout (DKO) mice are consistent with, and probably result from, elevated DEVDase and VEIDase activities, corresponding to caspase 3 and caspase 6, respectively. Immunofluorescence microscopy revealed an increased amount of caspase 6, and the active form of caspase 3, in specific regions of the DKO lens, coincident with the site of cell disintegration. TUNEL labeling illustrated a higher level of DNA fragmentation in the secondary fiber lens cells of DKO mice, compared with wild-type mice. Using a pull-down assay, we show interaction between caspase 6 and {alpha}A- but not {alpha}B-crystallin. These studies suggest that {alpha}-crystallin plays a role in suppressing caspase activity, resulting in retention of lens fiber cell integrity following degradation of mitochondria and other organelles, which occurs during the apoptosis-like pathway of lens cell terminal differentiation.
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