Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption

Dennis M. Marcus, Anil K. Rustgi, Dennis Defoe, Steven E. Brooks, Robert S. McCormick, Todd P. Thompson, Winfried Edelmann, Raju Kucherlapati, Sylvia Smith

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)645-650
Number of pages6
JournalArchives of Ophthalmology
Volume115
Issue number5
StatePublished - 1997

Fingerprint

APC Genes
Retinal Pigment Epithelium
Adenomatous Polyposis Coli
Codon
Retina
Coloboma
Mutation
Hypertrophy
Atrophy
Hyperplasia

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Marcus, D. M., Rustgi, A. K., Defoe, D., Brooks, S. E., McCormick, R. S., Thompson, T. P., ... Smith, S. (1997). Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption. Archives of Ophthalmology, 115(5), 645-650.

Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption. / Marcus, Dennis M.; Rustgi, Anil K.; Defoe, Dennis; Brooks, Steven E.; McCormick, Robert S.; Thompson, Todd P.; Edelmann, Winfried; Kucherlapati, Raju; Smith, Sylvia.

In: Archives of Ophthalmology, Vol. 115, No. 5, 1997, p. 645-650.

Research output: Contribution to journalArticle

Marcus, DM, Rustgi, AK, Defoe, D, Brooks, SE, McCormick, RS, Thompson, TP, Edelmann, W, Kucherlapati, R & Smith, S 1997, 'Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption', Archives of Ophthalmology, vol. 115, no. 5, pp. 645-650.
Marcus DM, Rustgi AK, Defoe D, Brooks SE, McCormick RS, Thompson TP et al. Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption. Archives of Ophthalmology. 1997;115(5):645-650.
Marcus, Dennis M. ; Rustgi, Anil K. ; Defoe, Dennis ; Brooks, Steven E. ; McCormick, Robert S. ; Thompson, Todd P. ; Edelmann, Winfried ; Kucherlapati, Raju ; Smith, Sylvia. / Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption. In: Archives of Ophthalmology. 1997 ; Vol. 115, No. 5. pp. 645-650.
@article{98747c4255c2487696adf2171ad8663e,
title = "Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption",
abstract = "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.",
author = "Marcus, {Dennis M.} and Rustgi, {Anil K.} and Dennis Defoe and Brooks, {Steven E.} and McCormick, {Robert S.} and Thompson, {Todd P.} and Winfried Edelmann and Raju Kucherlapati and Sylvia Smith",
year = "1997",
language = "English (US)",
volume = "115",
pages = "645--650",
journal = "JAMA Ophthalmology",
issn = "2168-6165",
publisher = "American Medical Association",
number = "5",

}

TY - JOUR

T1 - Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption

AU - Marcus, Dennis M.

AU - Rustgi, Anil K.

AU - Defoe, Dennis

AU - Brooks, Steven E.

AU - McCormick, Robert S.

AU - Thompson, Todd P.

AU - Edelmann, Winfried

AU - Kucherlapati, Raju

AU - Smith, Sylvia

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031000341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031000341&partnerID=8YFLogxK

M3 - Article

VL - 115

SP - 645

EP - 650

JO - JAMA Ophthalmology

JF - JAMA Ophthalmology

SN - 2168-6165

IS - 5

ER -