Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice.
Document Type
Article
Publication Date
2001
Keywords
Cell-Count, Cell-Differentiation, Cell-Division, Cones-(Retina), Female, Fundus-Oculi, Gene-Expression-Profiling, Genotype, Human, Immunohistochemistry, Male, Mice, Mice-Inbred-C57BL, Mutation, Phenotype, Receptors-Cytoplasmic-and-Nuclear, Retina, Retinal-Degeneration, Retinal-Dysplasia, SUPPORT-U-S-GOVT-P-H-S, Transcription-Factors
First Page
1619
Last Page
1626
JAX Source
Hum Mol Genet 2001 Aug; 10(16):1619-26.
Grant
CA34196/CA/NCI, EY11996/EY/NEI, T32HD07065-21/HD/NICHD
Abstract
The rd7 mouse is a model for hereditary retinal degeneration characterized clinically by retinal spotting throughout the fundus and late onset retinal degeneration, and histologically by retinal dysplasia manifesting as folds and whorls in the photoreceptor layer. This study demonstrates that the rd7 phenotype results from a splicing error created by a genomic deletion of an intron and part of an exon. Hematoxylin/eosin staining of rd7 tissue shows that the whorls in the outer nuclear layer of the retina do not appear during embryonic development but manifest by postnatal day 12.5 (P12.5). Furthermore, in situ hybridization data indicates that the Nr2e3 message is first present at barely discernable levels at embryonic day 18.5, becomes abundant by P2.5, and reaches maximal adult levels by P10.5. Results from these experiments indicate that Nr2e3 message is expressed prior to the development of S-cones. This data coincides with studies in humans showing that mutations in Nr2e3 result in a unique type of retinal degeneration known as enhanced S-cone syndrome, where patients have a 30-fold increase in S-cone sensitivity compared to normal. Immunohistochemical staining of cone cells demonstrates that rd7 retinas have an increased number of cone cells compared to wild-type retinas. Thus, Nr2e3 may function by regulating genes involved in cone cell proliferation, and mutations in this gene lead to retinal dysplasia and degeneration by disrupting normal photoreceptor cell topography as well as cell-cell interactions.
Recommended Citation
Haider NB,
Naggert JK,
Nishina PM.
Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice. Hum Mol Genet 2001 Aug; 10(16):1619-26.