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

Nature Genetics volume 25, pages 67–73 (2000)Cite this article

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 oligomers1,2,3. Disk rims are thought to be critical for disk morphogenesis, OS renewal4 and the maintenance of OS structure5, 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 degeneration7, 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.

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Figure 1: Generation of Rom1-mutant mice.
Figure 2: Complete loss of Rom-1 results in apoptotic rod photoreceptor death.
Figure 3: The loss of Rom-1 leads to the development of short ROSs, which exhibit a biphasic pattern of disorganization.
Figure 4: ROS ultrastructure is abnormal in Rom1−/− mice, whereas cone OSs appear structurally normal.
Figure 5: Electroretinographic responses are abnormal in Rom1−/− mice.
Figure 6: Homotetramers of peripherin-2 are localized at the rims of ROS in Rom1-mutant mice.

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Acknowledgements

We thank J.G. Hollyfield, D. Bok, A. Aguirre and S. Fisher for helpful comments; J. Saari for the RDH-E6 anti-peripherin-2 antibody; G.H. Travis for the anti-peripherin-2 antibody D2P4; J. Nathans for the 2379 antibody to the Abcr protein; and B. Calvieri, D. Gross and I. Diplock for technical assistance. This work was supported by the Foundation Fighting Blindness (R.R.M.), the RP Eye Research Foundation of Canada (R.R.M. and R.S.M.), the NEI (EY02422) (R.S.M.), the Medical Research Council (Canada) (R.S.M. and J.R.) and the Canadian Genetic Disease Network (R.R.M.). G.C. was a recipient of a RP Eye Research Foundation of Canada Studentship. R.R.M. and J.R. are International Research Scholars of the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Program in Developmental Biology, The Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada

    Geoff Clarke, Danka Vidgen, Leslie Collins, Lynda Ploder & Roderick R. McInnes

  2. Program in Genetics, The Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada

    Geoff Clarke, Danka Vidgen, Leslie Collins, Lynda Ploder & Roderick R. McInnes

  3. Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada

    Roderick R. McInnes

  4. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada

    Geoff Clarke, Janet Rossant & Roderick R. McInnes

  5. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada

    Andrew F.X. Goldberg, Laurie L. Molday & Robert S. Molday

  6. Samuel Lunenfeld Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada

    Lois Schwarz & Janet Rossant

  7. Second Department of Anatomy, Histology and Embryology Laboratory of Electron Microscopy, Semmelweis University Medical School, Budapest, Hungary

    Ágoston Szél

  8. Retina Foundation of the Southwest, Dallas , Texas, USA

    David G. Birch

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Correspondence to Roderick R. McInnes.

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Clarke, G., Goldberg, A., Vidgen, D. et al. Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Nat Genet 25, 67–73 (2000). https://doi.org/10.1038/75621

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