Faculty Collaboration Database

174delG mutation in mouse MFRP causes photoreceptor degeneration and RPE atrophy. Invest Ophthalmol Vis Sci 2011 Sep 14;52(10):7256-66

Date

08/04/2011

Pubmed ID

21810984

Pubmed Central ID

PMC3207726

DOI

10.1167/iovs.11-8112

Scopus ID

2-s2.0-80655148211 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

PURPOSE: The authors have identified a recessive mutation causing progressive retinal degeneration, white fundus flecks, and eventual retinal pigment epithelium (RPE) atrophy. The goal of these studies was to characterize the retinal phenotype, to identify the causative locus, and to examine possible functions of the affected gene.

METHODS: SNP mapping, DNA sequencing, and genetic complementation were used to identify the affected locus. Histology, electroretinography, immunohistochemistry, Western blot analysis, fundus photography, electron microscopy, and in vitro phagocytosis assays were used to characterize the phenotype of the mouse.

RESULTS: Gene mapping identified a single base pair deletion in membrane-type frizzled related protein (MFRP), designated Mfrp(174delG). MFRP is normally expressed in the RPE and ciliary body but was undetectable by Western blot in mutants. CTRP5, a binding partner of MFRP, was upregulated at the mRNA level and at the protein level in most patients. Assays designed to test the integrity of retinoid cycling and phagocytic pathways showed no deficits in Mfrp(174delG) or rd6 animals. However, the RPE of both Mfrp(174delG) and rd6 mice exhibited a dramatic increase in the number of apical microvilli. Furthermore, evidence of RPE atrophy was evident in Mfrp(174delG) mice by 21 months.

CONCLUSIONS: The authors have identified a novel null mutation in mouse Mfrp. This mutation causes photoreceptor degeneration and eventual RPE atrophy, which may be related to alterations in the number of RPE microvilli. These mice will be useful to identify a function of MFRP and to study the pathogenesis of atrophic macular degeneration.

Author List

Fogerty J, Besharse JC

MESH terms used to index this publication - Major topics in bold

Animals
Atrophy
Base Sequence
Blotting, Western
Electroretinography
Eye Proteins
Immunohistochemistry
Membrane Proteins
Mice
Mice, Inbred C57BL
Microscopy, Electron
Phenotype
Photoreceptor Cells, Vertebrate
Polymorphism, Single Nucleotide
Retinal Degeneration
Retinal Pigment Epithelium
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Sequence Deletion