DOI: 10.1073/pnas.94.3.884. Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin

Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin

10.1073/pnas.94.3.884

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

αA-crystallin (αA) and αB-crystallin (αB) are among the predominant proteins of the vertebrate eye lens. In vitro , the α-crystallins, which are isolated together as a high molecular mass aggregate, exhibit a number of properties, the most interesting of which is their ability to function as molecular chaperones for other proteins. Here we begin to examine the in vivo functions of α-crystallin by generating mice with a targeted disruption of the αA gene. Mice that are homozygous for the disrupted allele produce no detectable αA in their lenses, based on protein gel electrophoresis and immunoblot analysis. Initially, the αA-deficient lenses appear structurally normal, but they are smaller than the lenses of wild-type littermates. αA −/− lenses develop an opacification that starts in the nucleus and progresses to a general opacification with age. Light and transmission electron microscopy reveal the presence of dense inclusion bodies in the central lens fiber cells. The inclusions react strongly with antibodies to αB but not significantly with antibodies to β- or γ-crystallins. In addition, immunoblot analyses demonstrate that a significant portion of the αB in αA −/− lenses shifts into the insoluble fraction. These studies suggest that αA is essential for maintaining lens transparency, possibly by ensuring that αB or proteins closely associated with this small heat shock protein remain soluble.

Bibliography

Brady, J. P., Garland, D., Duglas-Tabor, Y., Robison, W. G., Groome, A., & Wawrousek, E. F. (1997). Targeted disruption of the mouse Î±A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shockâproteinâÎ±B-crystallin. Proceedings of the National Academy of Sciences, 94(3), 884â889.

Authors 6

James P. Brady (first)
Donita Garland (additional)
Yvonne Duglas-Tabor (additional)
W. Gerald Robison (additional)
Anne Groome (additional)
Eric F. Wawrousek (additional)

References 31 Referenced 247

10.1364/AO.10.000459
10.1111/j.1432-0436.1981.tb01141.x
W W de Jong Molecular and Cellular Biology of the Eye Lens, ed H Bloemendal (Wiley, New York), pp. 221–278 (1981). / Molecular and Cellular Biology of the Eye Lens by de Jong W W (1981)
10.1016/S0021-9258(18)42574-4
10.1016/S0021-9258(18)50096-X
10.1016/S0021-9258(19)89469-3
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10.1128/mcb.9.3.1083-1091.1989
10.1073/pnas.79.7.2360
10.1073/pnas.88.9.3652
10.1016/0014-4835(92)90058-Z
J Horwitz, M McFall-Nagai, L L Ding, O Yaron The Lens: Transparency and Cataract, ed G Duncan (Eurage, Rijswijk, The Netherlands), pp. 227–240 (1986). / The Lens: Transparency and Cataract by Horwitz J (1986)
10.1016/0014-5793(88)80295-3
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10.3109/02713689209033490
10.1007/BF00221054
10.1111/j.1432-1033.1996.0056r.x
10.1002/j.1460-2075.1994.tb06339.x
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R I Larsson Immunocytochemistry: Theory and Practice (CRC, Boca Raton, FL, 1988). / Immunocytochemistry: Theory and Practice by Larsson R I (1988)
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10.1093/oxfordjournals.jbchem.a123665
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10.1242/jcs.108.4.1397

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:03 p.m.)
Indexed	4 days, 3 hours ago (Aug. 28, 2025, 8:26 a.m.)
Issued	28 years, 6 months ago (Feb. 4, 1997)
Published	28 years, 6 months ago (Feb. 4, 1997)
Published Online	28 years, 6 months ago (Feb. 4, 1997)
Published Print	28 years, 6 months ago (Feb. 4, 1997)

Funders 0

None

BibTeX

@article{Brady_1997, title={Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.3.884}, DOI={10.1073/pnas.94.3.884}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Brady, James P. and Garland, Donita and Duglas-Tabor, Yvonne and Robison, W. Gerald and Groome, Anne and Wawrousek, Eric F.}, year={1997}, month=feb, pages={884–889} }

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