The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
Mfrp, a gene encoding a frizzled related protein, is mutated in the mouse retinal degeneration 6
Abstract
The autosomal recessive mouse mutation retinal degeneration 6 (rd6) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolog of the human membrane-type frizzled-related protein (Mfrp) gene that results in the skipping of exon 4. We found that mRNA of Mfrp is predominantly expressed in the eye, and at a lower level in the brain. To determine where in the eye Mfrp is expressed, in situ hybridization was done and showed that Mfrp is expressed specifically in the retinal pigment epithelium (RPE) and ciliary epithelium of the eye. The deduced amino acid sequence of MFRP contains a region with similarities to the cysteine-rich domain (CRD) of frizzled, a gene originally found in Drosophila that controls tissue polarity. The CRD is essential for Wnt binding and signaling. Wnt signaling has been shown to be involved in the control of gene expression, cell adhesion, planar polarity, proliferation and apoptosis. We also observed the localization of Wnt family proteins in the apical membrane of the RPE. Our results provide genetic evidence for an involvement of the Mfrp gene expressed by RPE in the degeneration of photoreceptors.
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In the citing paper
“abnormal Wnt/frizzled signaling in the RPE may be responsible for photoreceptor degeneration”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Kameya et al., 2002
In the citing paper
“Aberrations in the Wnt/frizzled signaling pathway have been implicated in photoreceptor degeneration in retinitis pigmentosa patients”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Kameya et al., 2002
In the citing paper
“The photoreceptor layer degenerates to 33% of its original thickness by 4.5 months of age, 15% of normal by 7 months of age, and becomes 1 cell layer thick by 24 months of age”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Kameya et al., 2002
In the citing paper
“has strong homology to the cysteine-rich domain of frizzled, a protein that is an important member of the Wnt family of proteins”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Kameya et al., 2002
In the citing paper
“Mfrp, expressed at high levels exclusively in the RPE and ciliary epithelium and not the neural retina”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Kameya et al., 2002
In the citing paper
“A splice-donor mutation with the loss of an exon in a gene encoding membrane-type frizzled protein (Mfrp) was identified in the rd6 mouse”
From Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD) (2010) · cites this paper as Kameya et al., 2002
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Metadata
- Authors
- Kameya, S.
- Affiliations
- Jackson Laboratory (US)
- Corresponding author
- Kameya, S.
- ORCID
- Kameya, S.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-08-01
- Volume
- 11
- Issue
- 16
- Pages
- 1879-1886
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2111852904
- Cited by
- 134
- References
- 41
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ey012093-03)
- National Eye Institute (EY 11996, EY12093, R01EY011996)
- National Cancer Institute (#CA34196, P30CA034196)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- MFRP, photoreceptor degeneration, retinal pigment epithelium, ciliary epithelium, Wnt signaling, cysteine-rich domain, splice donor mutation, exon skipping, positional cloning
- MeSH terms
- Frizzled-Related Proteins, Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Disease Models, Animal, DNA, Eye Proteins, Humans, Membrane Proteins, Mice, Mutant Strains, Molecular Sequence Data, Mutation, Retinal Degeneration, Gene Expression, Sequence Homology, Amino Acid, In Situ Hybridization, Mice
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