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Updated: Jun 15, 2026
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Analysis of genes differentially expressed during retinal degeneration in three mouse models
Yogita Kanan1, Michael Centola, Frank Bart
1Department of Cell Biology, BMSB 781, Oklahoma City, OK 73104, USA.
Abstract:
An estimated 100,000 people in the US alone have retinitis pigmentosa. This disease, caused by the loss of rods and cones, results in blindness. With the intention of identifying common cell death pathways that result in RP, the pattern of global gene expression in three different mouse models of retinal degeneration was analyzed using DNA arrays. The models used were opsin ( Delta255-256 ), a transgenic mouse line that expresses a mutant form of opsin with a deletion of an isoleucine at either position 255 or 256; the Bouse C mouse, whereby normal opsin is over-expressed by over 2 folds; MOT1, a model that expresses SV-40 T antigen downstream of opsin promoter and leads to retinal degeneration. We found that, at least in the 2 models of retinal degeneration that are characterized by rhodopsin abnormalities, death is due to the TNF pathway. In addition, there are a number of unknown genes not yet annotated in each of the models that could be promising in revealing novel functions in photoreceptors.
Insights
Retinitis pigmentosa (RP) causes blindness due to photoreceptor loss. This study found the TNF pathway involved in cell death in two RP mouse models, suggesting potential therapeutic targets.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Retinitis pigmentosa (RP) affects approximately 100,000 individuals in the US, leading to blindness through photoreceptor degeneration.
- Understanding the molecular mechanisms of cell death in RP is crucial for developing effective treatments.
Purpose of the Study:
- To identify common cell death pathways implicated in retinitis pigmentosa.
- To analyze gene expression patterns in mouse models of retinal degeneration.
Main Methods:
- Global gene expression analysis using DNA arrays was performed on three distinct mouse models of retinal degeneration.
- Models included opsin (Delta255-256) mutant mice, Bouse C mice with opsin overexpression, and MOT1 mice expressing SV-40 T antigen.
Main Results:
- The Tumor Necrosis Factor (TNF) pathway was identified as a key mediator of cell death in two models characterized by rhodopsin abnormalities.
- Analysis revealed numerous unannotated genes in each model, potentially indicating novel photoreceptor functions.
Conclusions:
- The TNF pathway plays a significant role in photoreceptor cell death in specific models of retinitis pigmentosa.
- Further investigation of unannotated genes may uncover new therapeutic targets and insights into photoreceptor biology.
