ArticlePloS one2012
The LEGSKO mouse: a mouse model of age-related nuclear cataract based on genetic suppression of lens glutathione synthesis.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- Proteomic Characterization of the Rhesus Macaque Lens Nucleus: Similarity to Human Lens, Age Effects on Protein Solubility, and Trends in Post-Translational Modifications.Investigative ophthalmology & visual science · 2025Article
- Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract.Antioxidants (Basel, Switzerland) · 2024Review
- Aging of the eye: Lessons from cataracts and age-related macular degeneration.Ageing research reviews · 2024Review
- Prevention of age-related truncation of γ-glutamylcysteine ligase catalytic subunit (GCLC) delays cataract formation.Science advances · 2024Article
- Application of transgenic mice to the molecular pathogenesis of cataract.International journal of ophthalmology · 2024Review
- Redox Regulation in Age-Related Cataracts: Roles for Glutathione, Vitamin C, and the NRF2 Signaling Pathway.Nutrients · 2023Review
- Role of Oxidative Stress in Ocular Diseases: A Balancing Act.Metabolites · 2023Review
- A tamoxifen-inducible Cre knock-in mouse for lens-specific gene manipulation.Experimental eye research · 2023Article
- Oxidation of active cysteines mediates protein aggregation of S10R, the cataract-associated mutant of mouse GammaB-crystallin.Proteins · 2022Article
- Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts.Investigative ophthalmology & visual science · 2021Article
- Mitotic Activation Around Wound Edges and Epithelialization Repair in UVB-Induced Capsular Cataracts.Investigative ophthalmology & visual science · 2021Article
- Impaired GSH biosynthesis disrupts eye development, lens morphogenesis and PAX6 function.The ocular surface · 2021Article
- Examining the effects of cigarette smoke on mouse lens through a multi OMIC approach.Scientific reports · 2021Article
- Aging lens epithelium is susceptible to ferroptosis.Free radical biology & medicine · 2021Article
- Do Connexin Mutants Cause Cataracts by Perturbing Glutathione Levels and Redox Metabolism in the Lens?Biomolecules · 2020Article
- Oral intake of α‑glucosyl‑hesperidin ameliorates selenite‑induced cataract formation.Molecular medicine reports · 2020Article
- Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1.The Journal of biological chemistry · 2020Article
- Proteomic analysis of the glutathione-deficient LEGSKO mouse lens reveals activation of EMT signaling, loss of lens specific markers, and changes in stress response proteins.Free radical biology & medicine · 2017Article
- Reduced Glutathione Level Promotes Epithelial-Mesenchymal Transition in Lens Epithelial Cells via a Wnt/β-Catenin-Mediated Pathway: Relevance for Cataract Therapy.The American journal of pathology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Age-related nuclear cataracts are associated with progressive post-synthetic modifications of crystallins from various physical chemical and metabolic insults, of which oxidative stress is a major factor. The latter is normally suppressed by high concentrations of glutathione (GSH), which however are very low in the nucleus of the old lens. Here we generated a mouse model of oxidant stress by knocking out glutathione synthesis in the mouse in the hope of recapitulating some of the changes observed in human age-related nuclear cataract (ARNC). A floxed Gclc mouse was generated and crossed with a transgenic mouse expressing Cre in the lens to generate the LEGSKO mouse in which de novo GSH synthesis was completely abolished in the lens. Lens GSH levels were reduced up to 60% in homozygous LEGSKO mice, and a decreasing GSH gradient was noticed from cortical to nuclear region at 4 months of age. Oxidation of crystallin methionine and sulfhydryls into sulfoxides was dramatically increased, but methylglyoxal hydroimidazolones levels that are GSH/glyoxalase dependent were surprisingly normal. Homozygous LEGSKO mice developed nuclear opacities starting at 4 months that progressed into severe nuclear cataract by 9 months. We conclude that the LEGSKO mouse lens mimics several features of human ARNC and is thus expected to be a useful model for the development of anti-cataract agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.