|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 26 January 2006
doi: 10.1242/dev.02262
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  Y. Munemasa, J. M. K. Kwong, J. Caprioli, and N. Piri The Role of {alpha}A- and {alpha}B-Crystallins in the Survival of Retinal Ganglion Cells after Optic Nerve Axotomy Invest. Ophthalmol. Vis. Sci., August 1, 2009; 50(8): 3869 - 3875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang, J. Li, C. Huang, L. Xue, Y. Peng, Q. Fu, L. Gao, J. Zhang, and W. Li Targeted Knockout of the Mouse {beta}B2-crystallin Gene (Crybb2) Induces Age-Related Cataract Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5476 - 5483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
