Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis

The homologous membrane proteins Rom-1 and peripherin-2 are localized to th e disk rims of photoreceptor outer segments (OSs), where they associate as tetramers and larger oligomers(1-3). Disk rims are thought to be critical f or disk morphogenesis, OS renewal(4) and the maintenance of OS structure(5) , but the molecules which regulate these processes are unknown. Although pe ripherin-2 is known to be required for OS formation (because Prph2(-/-) mic e do not form OSs; ref. 6), and mutations in RDS (the human homologue of Pr ph2) cause retinal degeneration(7), the relationship of Rom-1 to these proc esses is uncertain. Here we show that Rom1(-/-) mice form OSs in which peri pherin-2 homotetramers are localized to the disk rims, indicating that peri pherin-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 sl owly by apoptosis. Furthermore, the maximal photoresponse of Rom1(-/-) rod photoreceptors was lower than that of controls. We conclude that Rom-1 is r equired for the regulation of disk morphogenesis and the viability of mamma lian rod photoreceptors, and that mutations in human ROM1 may cause recessi ve photoreceptor degeneration.