Marcus D M, Rustgi A K, Defoe D, Kucherlapati R, Edelmann W, Hamasaki D, Liou G I, Smith S B
Department of Ophthalmology, Medical College of Georgia, Augusta, GA, USA.
Mol Vis. 2000 Sep 8;6:169-77.
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.
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.
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.
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.
为了继续之前对密码子1638处腺瘤性息肉病大肠杆菌（APC）基因突变小鼠眼睛的形态学研究，我们确定了这些眼睛的超微结构和电生理特征。
对20只APC基因杂合突变小鼠的38只眼睛和11只野生型小鼠的22只眼睛进行了光学显微镜检查。对6只无光学显微镜异常的APC修饰眼睛、4只伴有局灶性光学显微镜异常的APC修饰眼睛和4只野生型眼睛进行了电子显微镜检查。对4只APC修饰小鼠和3只野生型小鼠记录了视网膜电图。
38只APC修饰眼睛中有4只显示出局部视网膜色素上皮（RPE）细胞超微结构证据，表现为黑素体生成增加和萎缩。这4只眼睛中RPE的其他区域未显示超微结构异常。3只APC修饰眼睛显示出RPE增生的电子显微镜和光学显微镜证据。对无光学显微镜异常证据的APC修饰眼睛进行电子显微镜检查，结果显示与年龄匹配的对照无超微结构差异。视网膜电图显示，APC修饰小鼠和野生型小鼠之间的b波或c波振幅无差异。
虽然在这些APC修饰小鼠中观察到了光学显微镜下的RPE改变，但未发现普遍的超微结构小鼠RPE缺陷，这与对患有结肠息肉病、色素性眼底病变以及密码子463至1444之间APC基因突变的人类进行电子显微镜研究的观察结果形成对比。然而，我们对密码子1638处APC突变小鼠的研究结果与先前确定的人类APC基因中色素性眼底病变表达与区域特异性突变之间的关联一致。APC蛋白可能对视网膜和RPE的发育具有生理功能。
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