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Ultrastructural and ERG findings in mice with adenomatous polyposis coli gene disruption
D M Marcus1, A K Rustgi, D Defoe
1Department of Ophthalmology, Medical College of Georgia, Augusta, GA, USA. dmarcus@mail.mcg.edu
Purpose:
In order to continue the previous morphological studies of eyes from mice with adenomatous polyposis coli (APC) gene mutation at codon 1638, we determined the ultrastructural and electrophysiologic characteristics of these eyes.
Methods:
Thirty-eight eyes from 20 mice heterozygous for APC gene mutation and 22 eyes from 11 wild-type mice were examined by light microscopy. Six APC-modified eyes without light microscopic abnormalities, four APC-modified eyes with focal light microscopic abnormalities, and four wild-type eyes were examined by electron microscopy. Electroretinograms were recorded from four APC-modified and three wild-type mice.
Results:
Four of 38 APC-modified eyes demonstrated ultrastructural evidence of focal RPE cells with increased melanosome production and atrophy. Other areas of the RPE in these four eyes demonstrated no ultrastructural abnormalities. Three APC-modified eyes demonstrated electron and light microscopic evidence of RPE hyperplasia. Electron microscopic examination of APC-modified eyes without light microscopic evidence of abnormalities demonstrated no ultrastructural differences from age-matched controls. Electroretinography demonstrated no differences in the b-wave or c-wave amplitudes between APC-modified and wild-type mice.
Conclusions:
While light microscopic RPE alterations are observed in these APC-modified mice, the absence of a generalized, ultrastructural murine RPE defect is in contradistinction to observations in electron microscopic investigations of humans with colonic polyposis, pigmented ocular fundus lesions, and APC gene mutations between codons 463 and 1444. Our results in mice with APC mutation at codon 1638, however, are consistent with a previously identified association between the expression of pigmented ocular fundus lesions and region-specific mutation in the human APC gene. The APC protein may possess a physiologic function for both retinal and RPE development.
Insights
Mice with a specific adenomatous polyposis coli (APC) gene mutation showed some retinal pigment epithelium (RPE) changes but no generalized defect. These findings suggest APC gene region-specific mutations influence ocular development.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- The adenomatous polyposis coli (APC) gene is crucial in cellular function, and mutations are linked to various diseases, including colonic polyposis.
- Previous studies have explored the ocular manifestations of APC gene mutations, particularly in relation to pigmented fundus lesions.
Purpose of the Study:
- To investigate the ultrastructural and electrophysiologic characteristics of eyes from mice with an APC gene mutation at codon 1638.
- To compare these findings with wild-type mice and previous human studies.
Main Methods:
- Light and electron microscopy were used to examine 38 eyes from APC-mutated mice and 22 eyes from wild-type mice.
- Electroretinograms (ERGs) were recorded to assess retinal function in both groups.
Main Results:
- Ultrastructural analysis revealed focal retinal pigment epithelium (RPE) cell abnormalities, including increased melanosome production and atrophy, in some APC-mutated eyes.
- Evidence of RPE hyperplasia was observed in three APC-mutated eyes.
- No significant differences in ERG b-wave or c-wave amplitudes were found between APC-mutated and wild-type mice.
Conclusions:
- Despite observed focal RPE alterations, APC-mutated mice at codon 1638 did not exhibit a generalized ultrastructural RPE defect, unlike some human cases.
- These findings support an association between region-specific APC gene mutations and the development of pigmented ocular fundus lesions.
- The APC protein likely plays a role in both retinal and RPE development.