title: The K153Del PRPH2 mutation differentially impacts photoreceptor structure and function.
abstract: Peripherin 2 (Prph2) is a photoreceptor tetraspanin, and deletion of codon 153 (K153Δ) leads to retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in the same family. To study this variability, we generated a K153Δ-Prph2 knockin mouse. K153Δ-Prph2 cannot form the complexes required for outer segment formation, and in cones cannot interact with its binding partner rod outer segment membrane protein 1. K153Δ causes dominant defects in rod and cone function; however, rod but not cone ultrastructure is improved by the presence of K153Δ-Prph2. Likewise, supplementation of K153Δ heterozygotes with WT-Prph2 results in structural but not functional improvements. These results support the idea that mutations may differentially affect Prph2's role as a structural component, and its role as a functional protein key for organizing membrane domains for cellular signalling. These roles may be different in rods and cones, thus contributing to the phenotypic heterogeneity that characterizes diseases associated with Prph2 mutations.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Chakraborty
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, TX, USA.
authors.forename: Rahel
authors.initials: R
authors.lastname: Zulliger
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, TX, USA. mnaash@central.uh.edu.
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D000818:Animals; D003062:Codon / Q000235:genetics; D055879:Gene Knock-In Techniques; D006579:Heterozygote; D006801:Humans; D051379:Mice; D064531:Peripherins / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000648:ultrastructure; D017384:Sequence Deletion
chemical_list: D003062:Codon; C578997:PRPH2 protein, human; D064531:Peripherins; C578996:Prph2 protein, mouse