Cited by 134Retinal Development and DisordersRetinal Diseases and TreatmentsGenetic and Kidney Cyst Diseases

Mfrp, a gene encoding a frizzled related protein, is mutated in the mouse retinal degeneration 6

Kameya, S.·2002·Human Molecular Genetics

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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Crossref · 10.1093/hmg/11.16.1879

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Authors
Kameya, S.
Affiliations
Jackson Laboratory (US)
Corresponding author
Kameya, S.
Venue
Human Molecular Genetics
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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