title: Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis.
abstract: The homologous membrane proteins Rom-1 and peripherin-2 are localized to the disk rims of photoreceptor outer segments (OSs), where they associate as tetramers and larger oligomers. Disk rims are thought to be critical for disk morphogenesis, OS renewal and the maintenance of OS structure, but the molecules which regulate these processes are unknown. Although peripherin-2 is known to be required for OS formation (because Prph2-/- mice do not form OSs; ref. 6), and mutations in RDS (the human homologue of Prph2) cause retinal degeneration, the relationship of Rom-1 to these processes is uncertain. Here we show that Rom1-/- mice form OSs in which peripherin-2 homotetramers are localized to the disk rims, indicating that peripherin-2 alone is sufficient for both disk and OS morphogenesis. The disks produced in Rom1-/- mice were large, rod OSs were highly disorganized (a phenotype which largely normalized with age) and rod photoreceptors died slowly by apoptosis. Furthermore, the maximal photoresponse of Rom1-/- rod photoreceptors was lower than that of controls. We conclude that Rom-1 is required for the regulation of disk morphogenesis and the viability of mammalian rod photoreceptors, and that mutations in human ROM1 may cause recessive photoreceptor degeneration.
authors.affiliation: Program in Developmental Biology, The Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Clarke
authors.forename: A F
authors.initials: AF
authors.lastname: Goldberg
authors.forename: D
authors.initials: D
authors.lastname: Vidgen
authors.forename: L
authors.initials: L
authors.lastname: Collins
authors.forename: L
authors.initials: L
authors.lastname: Ploder
authors.forename: L
authors.initials: L
authors.lastname: Schwarz
authors.forename: L L
authors.initials: LL
authors.lastname: Molday
authors.forename: J
authors.initials: J
authors.lastname: Rossant
authors.forename: A
authors.initials: A
authors.lastname: Szél
authors.forename: R S
authors.initials: RS
authors.lastname: Molday
authors.forename: D G
authors.initials: DG
authors.lastname: Birch
authors.forename: R R
authors.initials: RR
authors.lastname: McInnes
mesh_terms: D000818:Animals; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009898:Optic Disk / Q000254:growth & development* / Q000648:ultrastructure; D064531:Peripherins; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology* / Q000648:ultrastructure; D012374:Rod Cell Outer Segment / Q000254:growth & development / Q000648:ultrastructure; D059470:Tetraspanins
chemical_list: D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; C578996:Prph2 protein, mouse; C513106:ROM1 protein, human; C081477:Rom1 protein, mouse; D059470:Tetraspanins