A Temperature-sensitive Mutation of Crygs in the Murine Opj Cataract

Debasish Sinha, M. Keith Wyatt, Robert Sarra, Cynthia Jaworski, Christine Slingsby, Caroline Thaung, Lewis Pannell, W. Gerald Robison, Jack Favor, Mary Lyon, Graeme Wistow

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9308-9315
Number of pages8
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Mar 23 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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