Association of hereditary cataracts in strain 13 N guinea-pigs with mutation of the gene for ζ-crystallin

Congenital nuclear cataracts transmitted by an autosomal dominant gene are present in a line of strain 13 N guinea-pigs. Studies on the lens proteins from these animals demonstrate changes in both the composition and structure of the crystallins relative to normal controls. The most prominent difference is in the ζ-crystallin, a taxon-specific crystallin which has been shown to be related to the alcohol dehydrogenases. In animals homozygous for the cataract phenotype the normal ζ-crystallin polypeptide is absent from the lens. Quantitation is difficult in the cataractous lenses from heterozygotes because of protein changes secondary to opacification: however in liver and kidney which have catalytic levels of the protein, the concentrations are approximately half that present in tissue from normal control animals. These findings suggest that in the cataractous animals a mutation has occurred in the gene for ζ-crystallin. In addition, a novel protein which is very similar to ζ-crystallin is synthesized only in the lenses of animals with cataract. This protein appears to be the product of the mutant gene for ζ-crystallin. These data support the hypothesis that this hereditary congenital cataract results from a specific mutation in the ζ-crystallin gene.