QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 26 January 2006
doi: 10.1242/dev.02262

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.02262v1 133/5/813    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morozov, V. Articles by Wawrousek, E. F. Search for Related Content PubMed PubMed Citation Articles by Morozov, V. Articles by Wawrousek, E. F.

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

Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Building 7, 7 Memorial Drive, MSC 0704 Bethesda, MD 20892, USA.

^* Author for correspondence (e-mail: morozovv{at}nei.nih.gov)

Accepted 21 December 2005

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 A-/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 A- but not B-crystallin. These studies suggest that -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.

Key words: Caspase 3, Caspase 6, A-crystallin, B-crystallin, Double knockout mice

Related articles in Development:

Vision clouded by apoptosis

Development 2006 133: e503. [Full Text]  

This article has been cited by other articles:

				N. A. Rao, S. Saraswathy, G. S. Wu, G. S. Katselis, E. F. Wawrousek, and S. Bhat Elevated Retina-Specific Expression of the Small Heat Shock Protein, {alpha}A-crystallin, Is Associated with Photoreceptor Protection in Experimental Uveitis Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 1161 - 1171. [Abstract] [Full Text] [PDF]

				J.-h. Xi, F. Bai, J. Gross, R. R. Townsend, A. S. Menko, and U. P. Andley Mechanism of Small Heat Shock Protein Function in Vivo: A KNOCK-IN MOUSE MODEL DEMONSTRATES THAT THE R49C MUTATION IN {alpha}A-CRYSTALLIN ENHANCES PROTEIN INSOLUBILITY AND CELL DEATH J. Biol. Chem., February 29, 2008; 283(9): 5801 - 5814. [Abstract] [Full Text] [PDF]

				A. Dimberg, S. Rylova, L. C. Dieterich, A.-K. Olsson, P. Schiller, C. Wikner, S. Bohman, J. Botling, A. Lukinius, E. F. Wawrousek, et al. {alpha}B-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis Blood, February 15, 2008; 111(4): 2015 - 2023. [Abstract] [Full Text] [PDF]

				A. J. Zandy and S. Bassnett Proteolytic Mechanisms Underlying Mitochondrial Degradation in the Ocular Lens Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 293 - 302. [Abstract] [Full Text] [PDF]