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Functional consequences of oncogene-induced photoreceptor degeneration in transgenic mice
N S Peachey1, Y Goto, A B Quiambao
1Department of Neurology, Stritch School of Medicine, Loyola University of Chicago, Maywood, USA.
Abstract:
This study evaluated retinal function in mice following the expression of oncogenes under the control of photoreceptor-specific promoters in transgenic mice. Electroretinograms (ERGs) were recorded under stimulus conditions chosen to elicit rod- or cone-mediated components. In one transgenic line (MOT1), the simian virus 40 large tumor antigen was expressed under the control of the mouse opsin promoter. MOT1 mice exhibited an age-related decline in the amplitude of the rod-mediated ERG a-wave. In comparison, cone-mediated responses recorded from MOT1 mice remained normal up to four months of age, the oldest age tested. In the second transgenic line (CMYC), the rat c-myc gene was expressed under control of the human interphotoreceptor-retinoid binding protein promoter. CMYC mice exhibited a rapid reduction of cone-mediated responses and a gradual loss of the rod ERG a-wave. Analysis of rod ERG a-waves obtained from young MOT1 and CMYC mice indicated that the rod ERG abnormalities reflect a reduction in the number of rods contributing to the response with the retention of normal response properties in rods that remain. These results support the possibility that aberrant expression of oncogenes may underlie some forms of human rod and cone-rod dystrophy.
Insights
This study investigated how oncogenes affect retinal function in mice. Aberrant oncogene expression in photoreceptors caused vision loss, suggesting a link to human retinal dystrophies.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Photoreceptor-specific promoters control gene expression in the retina.
- Oncogenes, when aberrantly expressed, can disrupt normal cellular function.
- Transgenic mouse models are crucial for studying retinal diseases.
Purpose of the Study:
- To evaluate the impact of oncogene expression on retinal function in mice.
- To investigate the role of specific oncogenes (SV40 large T-antigen and c-myc) in photoreceptor degeneration.
- To explore the potential link between oncogene-induced retinal dysfunction and human retinal dystrophies.
Main Methods:
- Generation of transgenic mice with photoreceptor-specific oncogene expression.
- Electrophysiological assessment using electroretinograms (ERGs) to measure rod and cone function.
- Analysis of ERG a-wave amplitudes to quantify rod and cone responses.
Main Results:
- Mice expressing simian virus 40 large tumor antigen (MOT1) showed age-related decline in rod-mediated ERG a-wave, while cone function remained normal.
- Mice expressing rat c-myc (CMYC) exhibited rapid loss of cone responses and gradual loss of rod ERG a-wave.
- Abnormalities in both lines suggest a reduced number of functional rods, not altered rod response properties.
Conclusions:
- Aberrant expression of oncogenes in photoreceptors leads to distinct patterns of retinal dysfunction in mice.
- These findings support the hypothesis that oncogene dysregulation may contribute to human rod and cone-rod dystrophies.
- Transgenic models provide valuable insights into the molecular mechanisms underlying inherited retinal diseases.
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