title: 174delG mutation in mouse MFRP causes photoreceptor degeneration and RPE atrophy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fogerty
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Besharse
mesh_terms: D000818:Animals; D001284:Atrophy; D001483:Base Sequence; D015153:Blotting, Western; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D000099274:Frizzled-Related Proteins
chemical_list: D005136:Eye Proteins; D008565:Membrane Proteins; C423368:Mfrp protein, mouse; D000099274:Frizzled-Related Proteins