Deletion mutation in an eye lens beta-crystallin. An animal model for inherited cataracts

• Published in: The Journal of biological chemistry Vol. 266; no. 11; pp. 6742 - 6746
• Main Authors: Chambers, C, Russell, P
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 15.04.1991; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Base Sequence; beta -crystallin; Biological and medical sciences; Cataract - genetics; Chromosome Deletion; Cloning, Molecular; Crystallins - genetics; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Gene Library; genes; Genes. Genome; Lens, Crystalline - physiology; Lens, Crystalline - physiopathology; Mice; Mice, Mutant Strains; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; Reference Values; Restriction Mapping; RNA - genetics; RNA - isolation & purification; Sequence Homology, Nucleic Acid; Cataract; Nucleotide sequence; Rodentia; Hereditary; Structure composition relationship; Open reading frame; Vertebrata; Mammalia; Crystallin; Complementary DNA; Mouse; Restriction map; Models; Mutation; Comparative study; Aminoacid sequence
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(20)89562-3

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.