Abstract
The photoreceptor disk membrane protein peripherin/rds is essential for the outer segment morphogenesis and integrity. Peripherin/rds associates with itself and with its homologue Rom-1 to form homo- and hetero-complexes, which are necessary for its structural role (Goldberg et al., 1995; Molday, 1998). More than seventy different pathogenic mutations in the peripherin/rds gene have been identified. These mutations are divided primarily into two categories: those associated with classic retinitis pigmentosa (RP), and those associated with various forms of macular dystrophy (MD). In fact, mutations in peripherin/rds account for 5–10% of RP causes, and is a major cause for MD (Kohl et al., 1998; Molday, 1998; http://www.sph.uth.tmc.edu/RetNet; http://www.retina-international.org/scinews/rdsmut.htm). Insights into the functional significance, structural role, and pathogenic effects of this protein have been accumulating considerably since its initial description; this is largely accomplished by the use of laboratory animal models. Use of transgenic or knock-out animals holds great potential for the investigation of retinal disease pathogenesis and the exploration of therapeutic interventions. Table 21.1 summarizes the animal models used to investigate the disease-causing mutations in peripherin/rds. In addition to the pathogenesis study, transgenic mouse and Xenopus laevis expressing the wild type peripherin/rds or the C-terminus have also been used to explore the structural and functional significance of the protein (Loewen et al., 2003; Ritter et al., 2004).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Apfelstedt-Sylla, E., Theischen, M., Ruther, K., Wedemann, H., Gal, A., and Zrenner, E., 1995, Extensive intrafamilial and interfamilial phenotypic variation among patients with autosomal dominant retinal dystrophy and mutations in the human RDS/peripherin gene, Br J Ophthalmol 79:28–34.
Ding, X.Q., Nour, M., Ritter, L.M., Goldberg, A.F., Fliesler, S.J., and Naash, M.I., 2004, The R172W mutation in peripherin/rds causes a cone-rod dystrophy in transgenic mice, Hum Mol Genet 13:2075–2087.
Dryja, T.P., Hahn, L.B., Kajiwara, K., and Berson, E.L., 1997, Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa, Invest Ophthalmol Vis Sci 38:1972–1982.
Ekstrom, U., Andreasson, S., Ponjavic, V., Abrahamson, M., Sandgren, O., Nilsson-Ehle, P., and Ehinger, B., 1998, A Swedish family with a mutation in the peripherin/RDS gene (Arg-172-Trp) associated with a progressive retinal degeneration, Ophthalmic Genet 19:149–156.
Goldberg, A.F., Moritz, O.L., and Molday, R.S., 1995, Heterologous expression of photoreceptor peripherin/rds and Rom-1 in COS-1 cells: assembly, interactions, and localization of multisubunit complexes, Biochemistry 34:14213–14219.
Jacobson, S.G., Cideciyan, A.V., Maguire, A.M., Bennett, J., Sheffield, V.C., and Stone, E.M., 1996, Preferential rod and cone photoreceptor abnormalities in heterozygotes with point mutations in the RDS gene, Exp Eye Res 63:603–608.
Kajiwara, K., Hahn, L.B., Mukai, S., Travis, G.H., Berson, E.L., and Dryja, T.P., 1991, Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa, Nature 354:480–483.
Kedzierski, W., Lloyd, M., Birch, D.G., Bok, D., and Travis, G.H., 1997, Generation and analysis of transgenic mice expressing P216L-substituted rds/peripherin in rod photoreceptors, Invest Ophthalmol Vis Sci 38:498–509.
Kedzierski, W., Nusinowitz, S., Birch, D., Clarke, G., McInnes, R.R., Bok, D., and Travis, G.H., 2001, Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa, Proc Natl Acad Sci U S A 98:7718–723.
Kedzierski, W., Weng, J., and Travis, G.H., 1999, Analysis of the rds/peripherin.rom1 complex in transgenic photoreceptors that express a chimeric protein, J Biol Chem 274:29181–29187.
Kohl, S., Giddings, I., Besch, D., Apfelstedt-Sylla, E., Zrenner, E., and Wissinger, B., 1998, The role of the peripherin/RDS gene in retinal dystrophies, Acta Anat (Basel) 162:75–84.
Li, C., Peachey, N.S., and Naash, M.I., 1999, Animal models with mutations in the peripherin/rds gene, Invest Ophthalmol Vis Sci 40:S202.
Loewen, C.J., Moritz, O.L., Tam, B.M., Papermaster, D.S., and Molday, R.S., 2003, The role of subunit assembly in peripherin-2 targeting to rod photoreceptor disk membranes and retinitis pigmentosa, Mol Biol Cell 14:3400–3413.
McNally, N., Kenna, P.F., Rancourt, D., Ahmed, T., Stitt, A., Colledge, W.H., Lloyd, D.G., Palfi, A., O’Neill, B., Humphries, M.M., et al., 2002, Murine model of autosomal dominant retinitis pigmentosa generated by targeted deletion at codon 307 of the rds-peripherin gene, Hum Mol Genet 11:1005–1016.
Milla, E., Heon, E., Piguet, B., Ducrey, N., Butler, N., Stone, E., Schorderet, D.F., and Munier, F., 1998, Mutational screening of peripherin/RDS genes, rhodopsin and ROM-1 in 69 index cases with retinitis pigmentosa and other retinal dystrophies, Klin Monatsbl Augenheilkd 212:305–308.
Molday, R.S., 1998, Photoreceptor membrane proteins, phototransduction, and retinal degenerative diseases. The Friedenwald Lecture, Invest Ophthalmol Vis Sci 39:2491–2513.
Nakazawa, M., Wada, Y., and Tamai, M., 1995, Macular dystrophy associated with monogenic Arg172Trp mutation of the peripherin/RDS gene in a Japanese family, Retina 15:518–523.
Nour, M., Ding, X.-Q., Stricker, H., Fliesler, S.J., and Naash, M.I., 2004, Modulating expression of peripherin/rds in transgenic mice: Critical levels and the effect of over-expression, Invest Ophthalmol Vis Sci 45:2514–2521.
Payne, A.M., Downes, S.M., Bessant, D.A., Bird, A.C., and Bhattacharya, S.S., 1998, Founder effect, seen in the British population, of the 172 peripherin/RDS mutation-and further refinement of genetic positioning of the peripherin/RDS gene, Am J Hum Genet 62:192–195.
Ritter, L.M., Boesze-Battaglia, K., Tam, B.M., Moritz, O.L., Khattree, N., Chen, S.C., and Goldberg, A.F., 2004, Uncoupling of photoreceptor peripherin/rds fusogenic activity from biosynthesis, subunit assembly, and targeting: a potential mechanism for pathogenic effects, J Biol Chem 279:39958–39967.
Saga, M., Mashima, Y., Akeo, K., Oguchi, Y., Kudoh, J., and Shimizu, N., 1993, A novel Cys-214-Ser mutation in the peripherin/RDS gene in a Japanese family with autosomal dominant retinitis pigmentosa, Hum Genet 92:519–521.
Stricker, H.M., Ding, X.-Q., Quiambao, A.B., and Naash, M.I., 2003, The C214S mutation in peripherin/rds confers protein instability, Protein Science 12(suppl.):111.
Tam, B.M., Moritz, O.L., and Papermaster, D.S., 2004, The C terminus of peripherin/rds participates in rod outer segment targeting and alignment of disk incisures, Mol Biol Cell 15:2027–2037.
Wells, J., Wroblewski, J., Keen, J., Inglehearn, C., Jubb, C., Eckstein, A., Jay, M., Arden, G., Bhattacharya, S., Fitzke, F., et al., 1993, Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy, Nat Genet 3:213–218.
Wroblewski, J.J., Wells, J.A., 3rd, Eckstein, A., Fitzke, F., Jubb, C., Keen, T.J., Inglehearn, C., Bhattacharya, S., Arden, G.B., Jay, M., et al., 1994, Macular dystrophy associated with mutations at codon 172 in the human retinal degeneration slow gene, Ophthalmology 101:12–22.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer Science+Business Media, Inc.
About this paper
Cite this paper
Ding, XQ., Naash, M.I. (2006). Transgenic Animal Studies of Human Retinal Disease Caused by Mutations in Peripherin/RDS . In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 572. Springer, Boston, MA. https://doi.org/10.1007/0-387-32442-9_21
Download citation
DOI: https://doi.org/10.1007/0-387-32442-9_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-28464-4
Online ISBN: 978-0-387-32442-5
eBook Packages: MedicineMedicine (R0)