Crystallin γB-I4F mutant protein binds to α-crystallin and affects lens transparency

Abstract

A new mouse mutant line, Clapper, identified from N-ethyl-N-nitrosurea (ENU)-mutagenized mice, develops a dominant lamellar cataract. The cataract blocks the image of retinal fundus and transmits a fuzzy fluorescein image of retinal vasculature during angiography. The cataractous lens opacity decreases as the mice age. The Clapper mutation has been identified to be a missense mutation of the γB-crystallin gene that replaces the 4th isoleucine residue with a phenylalanine (γB-I4F). Unlike wild type γB, the γB-I4F mutant protein binds to α-crystallin to form high molecular weight complexes in vivo and in vitro. Circular dichroism measurements indicate that γB-I4F protein is less stable than wild type γB at high temperature. Darkly stained aggregates, enlarged interfiber spaces, and disorganized and smaller inner mature fibers were found in the regions of the cataract in homozygous Clapper mutant lenses. Thus, the lamellar cataract is likely due to the light-scattering effects of the enlarged interfiber spaces and protein aggregates caused by γB-I4F mutant proteins interacting with α-crystallin in the lens. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.