TY - JOUR
T1 - A Temperature-sensitive Mutation of Crygs in the Murine Opj Cataract
AU - Sinha, Debasish
AU - Wyatt, M. Keith
AU - Sarra, Robert
AU - Jaworski, Cynthia
AU - Slingsby, Christine
AU - Thaung, Caroline
AU - Pannell, Lewis
AU - Robison, W. Gerald
AU - Favor, Jack
AU - Lyon, Mary
AU - Wistow, Graeme
PY - 2001/3/23
Y1 - 2001/3/23
N2 - In Opj, an inherited cataract in mice, opacity is associated with a mutation in Crygs, the gene for γS-crystallin, the first mutation to be associated with this gene. A single base change causes replacement of Phe-9, a key hydrophobic residue in the core of the N-terminal domain, by serine. Despite this highly non-conservative change, mutant protein folds normally at low temperature. However, it exhibits a marked, concentration-dependent decrease in solubility, associated with loss of secondary structure, at close to physiological temperatures. This is reminiscent of processes thought to occur in human senile cataracts in which normal proteins become altered and aggregate. The Opj cataract is progressive and more severe in Opj/Opj than in Opj/+. Lens histology shows that whereas fiber cell morphology in Opj/+ mice is essentially normal, in Opj/Opj, cortical fiber cell morphology and the loss of maturing fiber cell nuclei are both severely disrupted from early stages. This may indicate a loss of function of γS-crystallin which would be consistent with ideas that members of the βγ-crystallin superfamily may have roles associated with maintenance of cytoarchitecture.
AB - In Opj, an inherited cataract in mice, opacity is associated with a mutation in Crygs, the gene for γS-crystallin, the first mutation to be associated with this gene. A single base change causes replacement of Phe-9, a key hydrophobic residue in the core of the N-terminal domain, by serine. Despite this highly non-conservative change, mutant protein folds normally at low temperature. However, it exhibits a marked, concentration-dependent decrease in solubility, associated with loss of secondary structure, at close to physiological temperatures. This is reminiscent of processes thought to occur in human senile cataracts in which normal proteins become altered and aggregate. The Opj cataract is progressive and more severe in Opj/Opj than in Opj/+. Lens histology shows that whereas fiber cell morphology in Opj/+ mice is essentially normal, in Opj/Opj, cortical fiber cell morphology and the loss of maturing fiber cell nuclei are both severely disrupted from early stages. This may indicate a loss of function of γS-crystallin which would be consistent with ideas that members of the βγ-crystallin superfamily may have roles associated with maintenance of cytoarchitecture.
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U2 - 10.1074/jbc.M010583200
DO - 10.1074/jbc.M010583200
M3 - Article
C2 - 11121426
AN - SCOPUS:0035937738
SN - 0021-9258
VL - 276
SP - 9308
EP - 9315
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -