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Exp Eye Res. 2015 Sep;138:104-13. doi: 10.1016/j.exer.2015.07.001. Epub 2015 Jul 4.

A conserved role of αA-crystallin in the development of the zebrafish embryonic lens.

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
2
Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. Electronic address: hassane.mchaourab@Vanderbilt.Edu.

Abstract

αA- and αB-crystallins are small heat shock proteins that bind thermodynamically destabilized proteins thereby inhibiting their aggregation. Highly expressed in the mammalian lens, the α-crystallins have been postulated to play a critical role in the maintenance of lens optical properties by sequestering age-damaged proteins prone to aggregation as well as through a multitude of roles in lens epithelial cells. Here, we have examined the role of α-crystallins in the development of the vertebrate zebrafish lens. For this purpose, we have carried out morpholino-mediated knockdown of αA-, αBa- and αBb-crystallin and characterized the gross morphology of the lens. We observed lens abnormalities, including increased reflectance intensity, as a consequence of the interference with expression of these proteins. These abnormalities were less frequent in transgenic zebrafish embryos expressing rat αA-crystallin suggesting a specific role of α-crystallins in embryonic lens development. To extend and confirm these findings, we generated an αA-crystallin knockout zebrafish line. A more consistent and severe lens phenotype was evident in maternal/zygotic αA-crystallin mutants compared to those observed by morpholino knockdown. The penetrance of the lens phenotype was reduced by transgenic expression of rat αA-crystallin and its severity was attenuated by maternal αA-crystallin expression. These findings demonstrate that the role of α-crystallins in lens development is conserved from mammals to zebrafish and set the stage for using the embryonic lens as a model system to test mechanistic aspects of α-crystallin chaperone activity and to develop strategies to fine-tune protein-protein interactions in aging and cataracts.

KEYWORDS:

Alpha-crystallin; Cataract; Chaperone; Lens development; Maternal transcript; Morpholino; Small heat shock protein; TALEN; Zebrafish

PMID:
26149094
PMCID:
PMC4638411
DOI:
10.1016/j.exer.2015.07.001
[Indexed for MEDLINE]
Free PMC Article

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