Disease relevance of MFRP

• In human and mouse genomes, the MFRP gene lies adjoining to the complement 1q tumor necrosis factor-related protein 5 (CTRP5/C1QTNF5) gene involved in causing retinal degeneration and abnormal lens zonules in human [1].
• Extreme hyperopia is the result of null mutations in MFRP, which encodes a Frizzled-related protein [2].
• Our data indicate that defects in MFRP could be responsible for syndromic forms of microphthalmos/retinal degeneration and that this gene is necessary for photoreceptor maintenance [3].
• The MFRP mRNA was undetectable in seven gastric cancer cell lines, seven brain tumor cell lines, and other eight tumor cell lines [4].
• A new autosomal recessive syndrome consisting of posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disc drusen is caused by a MFRP gene mutation [3].

High impact information on MFRP

• This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction-corrected vision, produce clinically normal electro-retinograms, and show only modest anomalies in the dark adaptation of photoreceptors [2].
• Thirdly, C1QTNF5 is shown to interact with the membrane-type frizzled related protein (MFRP), on the basis of yeast two-hybrid, protein pull-down and co-immunoprecipitation assays and RPE co-localization [5].
• 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 [6].
• 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 [6].
• In the albino mouse eye, MFRP is localized to the apical and basal membranes of RPE and ciliary epithelium (CE) [1].

Biological context of MFRP

• RESULTS: The Mfrp gene is specifically expressed in RPE and ciliary body (CB), and its expression starts during early stages of embryogenesis [1].
• MFRP molecular analysis disclosed a one base pair insertion in exon 5 (c.498_499insC) in all affected individuals, a mutation that predicts a truncated protein (P165fsX198) [3].
• The MFRP gene on 11q23 consisted of at least 13 exons [4].
• In addition to CRD, two tandem-repeats containing the Cubilin domain approximately the MFRP domain were present in the extracellular region of MFRP [4].
• For these reasons, we investigated MFRP as a candidate gene for a phenotype associated with mutations [7].

Anatomical context of MFRP

• CONCLUSIONS: MFRP is localized to the plasma membrane of CE and RPE, and colocalizes and interacts with CTRP5 indicating a functional relationship between these two proteins [1].
• Thus, MFRP with CRD might play key roles in medulla oblongata as a regulator of the WNT signaling pathway [4].
• Regional distribution of the MFRP mRNA in human brain was further investigated, and MFRP was found to be expressed strongly in medulla oblongata, and weakly in hippocampus and corpus callosum [4].
• MFRP is highly expressed in the retinal pigment epithelial cells of the eye [7].

Associations of MFRP with chemical compounds

• MFRP is a member of the frizzled-related protein family and contains a cysteine-rich domain essential for Wnt binding and signaling [7].

Other interactions of MFRP

• We have cloned and characterized MFRP and RNF26 genes at 11q23 [8].
• We demonstrated that this clinical association is caused by a mutation in MFRP, a gene previously implicated in isolated nanophthalmos [3].
• Ophthalmologic manifestations, fundus photographs, ultrasonographic (US) assessment, electroretinography (ERG), fluorescein retinal angiography (FA), Goldmann kinetic perimetry (GKP), and optical coherence tomography (OCT), as well as mutational status of MFRP and CHX10 genes in genomic DNA [3].
• ABCG4, NCAM, and Mfrp are candidate genes in this region that theoretically may be disrupted [9].
• Although MFRP was homologous to Corin, FZDs, and SFRPs in CRD, amino-acid identities between CRD in MFRP and CRDs in these molecules were less than 40% [4].

Analytical, diagnostic and therapeutic context of MFRP

• Interaction with CTRP5 was studied by immunoprecipitation and immunoblot analysis, using mouse eye and human retinal pigmented epithelium (RPE) choroid extracts and by expressing full-length CTRP5 and MFRP in a heterologous system [1].
• MFRP protein expression and distribution were studied by Western blot analysis, immunohistochemistry, and immunoelectron microscopy [1].
• Mutations in candidate genes were screened by sequencing. mRNA expression of CTRP5 and MFRP, which are bicistronic genes, was studied by semiquantitative RT-PCR (qRT-PCR) in various human tissues [10].
• The 4.0-kb MFRP was not detected by Northern blot analysis in normal tissues other than adult and fetal brain [4].
• Molecular cloning and characterization of MFRP, a novel gene encoding a membrane-type Frizzled-related protein [4].

References