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Targeted Disruption of the Mouse α A-crystallin Gene Induces Cataract and Cytoplasmic Inclusion Bodies Containing the Small Heat Shock Protein α B-crystallin

James P. Brady, Donita Garland, Yvonne Duglas-Tabor, W. Gerald Robinson, Anne Groome and Eric F. Wawrousek
Proceedings of the National Academy of Sciences of the United States of America
Vol. 94, No. 3 (Feb. 4, 1997), pp. 884-889
Stable URL: http://www.jstor.org/stable/41404
Page Count: 6
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Targeted Disruption of the Mouse α A-crystallin Gene Induces Cataract and Cytoplasmic Inclusion Bodies Containing the Small Heat Shock Protein α B-crystallin
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Abstract

α A-crystallin (α A) and α B-crystallin (α B) 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 α A gene. Mice that are homozygous for the disrupted allele produce no detectable α A in their lenses, based on protein gel electrophoresis and immunoblot analysis. Initially, the α A-deficient lenses appear structurally normal, but they are smaller than the lenses of wild-type littermates. α A-/- 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 α B but not significantly with antibodies to β - or γ -crystallins. In addition, immunoblot analyses demonstrate that a significant portion of the α B in α A-/- lenses shifts into the insoluble fraction. These studies suggest that α A is essential for maintaining lens transparency, possibly by ensuring that α B or proteins closely associated with this small heat shock protein remain soluble.

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