Lop12, a mutation in mouse Crygd causing lens opacity similar to human Coppock cataract

A new cataract mutation was discovered in an ongoing program to identify ne w mouse models of hereditary eye disease. Lens opacity 12 (Lop12) is a semi dominant mutation that results in an irregular nuclear lens opacity similar to the human Coppock cataract. Lop12 is associated with a small nonrecombi ning segment that maps to mouse Chromosome 1 close to the eye lens obsolesc ence mutation (Cryge(Cat2-Elo)), a member of the gamma-crystallin gene clus ter (Cryg). Using a systemic candidate gene approach to analyze the entire Cryg cluster, a G to A transition was found in exon 3 of Crygd associated w ith the Lop12 mutation and has been designated Crygd(Lop12). The mutation C rygd(Lop12) leads to the formation of an in-frame stop codon that produces a truncated protein of 156 amino acids. It is predicted that the defective gene product alters protein folding of the gamma-crystallin(s) and results in lens opacity. (C) 2000 Academic Press.