Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption
D. M. Marcus, A. K. Rustgi, D. Defoe, S. E. Brooks, R. S. McCormick, T. P. Thompson, W. Edelmann, R. Kucherlapati and S. Smith
Department 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.
