DELETION MUTATION IN AN EYE LENS BETA-CRYSTALLIN - AN ANIMAL-MODEL FOR INHERITED CATARACTS

The most prevalent proteins in the lens of the eye are called crystallins, and it is thought that aberrant crystallins may cause opacification of lens tissue. The Philly mouse, a strain with an inherited cataract, has an abnormal beta-B2-crystallin, the principal beta-crystallin in the mouse. The cDNA that codes for the beta-B2-crystallin protein has been cloned and sequenced from both the normal and the cataractous Philly mouse. The normal mouse beta-B2 cDNA is 756 nucleotides in length with 618 nucleotides of open reading frame. An in-frame deletion of 12 nucleotides has occurred in the Philly mouse cDNA, which results in the loss of 4 amino acids. The sequence of the mutant beta-B2 was analyzed against the reported structure of the normal bovine beta-B2-crystallin determined by x-ray crystallography. The region, in which the deletion of the amino acids occurs near the COOH terminus, is essential for the formation of the tertiary structure of the beta-B2-crystallin. The loss of these residues could explain the alterations that are seen with the Philly beta-B2 protein and may account for the instability of the Philly beta-B2 protein. This abnormal beta-B2-crystallin may be the cause of the cataract in this animal.