The Peripherin/rds Gene
Mutations in the gene encoding the disk rim specific protein, peripherin/rds, have been implicated in the pathogenesis of both autosomal dominant retinitis pigmentosa (ADRP) and various forms of macular dystrophy (MD). Peripherin/rds plays an important role in the morphogenesis and maintenance of the disk rim structure.This role is supported by interactions with other proteins. To better understand how these mutations lead to the development of disease, knowledge of the structure-function relationships of the peripherin/rds gene is needed.To facilitate these studies, genomic clones encoding the murine gene were isolated using bovine cDNA sequences as probes. Sequence analysis of clones that contained the entire coding sequence for mouse peripherin/rds revealed the exon-intron organization of the gene. The gene is composed of three exons (581, 247, and 213bp) and two introns. The first and second introns are 8.6 kb and 3.7 kb in size, respectively. Two major (1.6 and 2.7kb) and three minor (4.0, 5.5, 6.5kb) transcripts were detected on RNA blots. Several transcription start sites were mapped within 26 nucleotides located approximately 200bp upstream from the translation initiation site. However, the lengths of the 3’untranslated portion of the transcripts varied because of utilization of different polyadenylation signals.
KeywordsRetinal Degeneration Cone Photoreceptor Disk Membrane Macular Dystrophy Cone Dystrophy
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- 2.Connell, G., Molday, L.L., Reid, D., and Molday, R.S. (1991) Molecular structure and properties of peripherin/rds the normal product of the gene responsible for retinal degeneration in the rds mouse. In Retinal Degenerations. R. Anderson, J. Hollyfield, and M. LaVail, editors. CRC Press, Boca Raton. 467–477.Google Scholar
- 10.Cheng, T., Peachey, N.S., Li, S., Goto, Y., Cao, Y., and Naash, M.I. (1997) The effect of peripherin/rds haploinsufficiency on rod and cone photoreceptors. J. Neurosci 17, 1–11.Google Scholar
- 12.Travis, G.H. and Bok, D. (1993) A molecular characterization of the retinal degeneration slow (rds) mouse mutation. In Retinal Degeneration: Clinical and Laboratory Applications. J.G. Hollyfield, R.E. Anderson, and M.M. LaVail, editors. Plenum Press, New York & London. 219–230.Google Scholar
- 16.Wells, J. Wroblewski, J., Keen, J., Inglehearn, C., Jubb, C., Eckstein, A., Jay, M., Arden, G.B., Battacharya, S.S., Fitzke, F., and Bird, A.C. (1993). Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy. Nature Genet. 3:213–218.PubMedCrossRefGoogle Scholar
- 17.Weleber, R., Carr, R.E., Murphey, W., Sheffield, V., and Stone, E. (1993). Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene. Arch. Ophthalmol. 111:1531–1542.PubMedGoogle Scholar
- 20.Molday, R.S. (1994) Peripherin/rds and rom-1: molecular properties and role in photoreceptor cell degeneration. In Progress in retinal and eye research. N.N. Osborne and G.J. Chader, editors. Pergamon Press Ltd., Great Britain. 271–299.Google Scholar
- 24.Cheng, T., Al-Ubaidi, M.R., and Naash, M.I. (1997) Structural and developmental analysis of the mouse peripherin/rds gene. Som. Cell. Mol. Genet. 23, 165–183.Google Scholar
- 35.Li, C., Al-Ubaidi, M.R., and Naash, M.I. (1997) Isolation and characterization of the skate peripherin/rds gene. Invest. Ophthalmol. Vis. Sci. 38:S219.Google Scholar