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Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption
D M Marcus1, A K Rustgi, D Defoe
1Department of Ophthalmology, Medical College of Georgia, Augusta, USA.
Objective:
To examine eyes from mice with targeted adenomatous polyposis coli (APC) gene disruption to determine if retinal pigment epithelium (RPE) abnormalities replicate the human counterpart.
Methods:
Thirty-two eyes from 16 mice heterozygous for APC gene disruption (chain-termination mutation in codon 1638 of exon 15) and 12 control eyes were examined by light microscopy.
Results:
Fifteen of 32 eyes from 12 of 16 APC-disrupted mice demonstrated abnormalities of the RPE and retina. The RPE abnormalities included RPE coloboma, unifocal and multifocal RPE hypertrophy, RPE hyperplasia, and RPE duplication with invasion in the areas of outer and inner segments. Retinal abnormalities included outer nuclear layer duplication and outer nuclear layer atrophy. There were no RPE and retinal abnormalities seen in the control eyes.
Conclusions:
This study is consistent with the hypothesis that the APC gene is critical in the regulation of RPE proliferation and development. These findings also demonstrate that mutation of the APC gene in codon 1638, a location beyond the previously described critical region for human RPE abnormalities, leads to perturbation in the mouse RPE and retina. Further study of this murine model and the APC/RPE relationship may provide insight into regulatory mechanisms for RPE proliferation.
Insights
Adenomatous polyposis coli (APC) gene disruption in mice causes retinal pigment epithelium (RPE) abnormalities, suggesting APC’s critical role in RPE development and proliferation.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- The adenomatous polyposis coli (APC) gene is crucial for cellular regulation.
- Understanding APC's role in retinal pigment epithelium (RPE) development is vital.
Purpose of the Study:
- To investigate RPE abnormalities in mice with targeted APC gene disruption.
- To determine if these abnormalities mimic human RPE conditions.
Main Methods:
- Light microscopy examination of 32 eyes from APC-disrupted mice and 12 control eyes.
- Analysis of heterozygous mice with a specific APC gene mutation (codon 1638).
Main Results:
- 15 of 32 APC-disrupted eyes showed RPE and retinal abnormalities.
- Observed RPE issues included coloboma, hypertrophy, hyperplasia, and duplication.
- Retinal findings included outer nuclear layer duplication and atrophy.
Conclusions:
- The APC gene is critical for regulating RPE proliferation and development.
- APC gene mutation at codon 1638 perturbs mouse RPE and retina.
- This murine model offers insights into APC/RPE relationships and RPE proliferation regulation.