The LEGSKO mouse: a mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesis.

摘要: Age-related nuclear cataracts are associated with progressive post-synthetic modifications of crystallins from various physical chemical and metabolic insults, which oxidative stress is a major factor. The latter normally suppressed by high concentrations glutathione (GSH), however very low in the nucleus old lens. Here we generated mouse model oxidant knocking out synthesis hope recapitulating some changes observed human age-related cataract (ARNC). A floxed Gclc was crossed transgenic expressing Cre lens to generate LEGSKO de novo GSH completely abolished Lens levels were reduced up 60% homozygous mice, decreasing gradient noticed cortical region at 4 months age. Oxidation crystallin methionine sulfhydryls into sulfoxides dramatically increased, but methylglyoxal hydroimidazolones that GSH/glyoxalase dependent surprisingly normal. Homozygous mice developed opacities starting progressed severe 9 months. We conclude mimics several features ARNC thus expected be useful for development anti-cataract agents.