Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption
Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption
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DOI：
10.1001/archopht.1997.01100150647013
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发表时间：
1997-05-01
影响因子：
--
通讯作者：
Smith, S
中科院分区：
文献类型：
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作者：
Marcus, DM;Rustgi, AK;Smith, S
目的：检测APC基因突变小鼠的眼睛，以确定视网膜色素上皮（RPE）异常是否复制人视网膜色素上皮（RPE）异常。方法：对16只APC基因断裂杂合小鼠32只眼（第15外显子1638密码子链终止突变）和12只对照眼进行光镜观察。结果：16只apc破坏小鼠中12只32只眼中有15只出现RPE和视网膜异常。RPE异常包括RPE结肠、单灶性和多灶性RPE肥大、RPE增生、内外节段浸润的RPE重复。视网膜异常包括外核层复制和外核层萎缩。对照眼未见RPE和视网膜异常。结论：本研究与APC基因在RPE增殖发育调控中起关键作用的假设一致。这些发现还表明，密码子1638上APC基因的突变，超出了先前描述的人类RPE异常的关键区域，导致小鼠RPE和视网膜的扰动。进一步研究该小鼠模型及APC/RPE关系，可能有助于进一步了解RPE增殖的调控机制。
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.