Ablation of the X-linked retinitis pigmentosa 2 (Rp2) gene in mice results in opsin mislocalization and photoreceptor degeneration

Investigative Ophthalmology and Visual Science

Volumn 54, Issue 7, 2013, Pages 4503-4511

  Li, Linjing ^a   Khan, Naheed ^b   Hurd, Toby ^c   Ghosh, Amiya Kumar ^b   Cheng, Christiana ^d   Molday, Robert ^d   Heckenlively, John R ^b   Swaroop, Anand ^e   Khanna, Hemant ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^e NATIONAL EYE INSTITUTE   (United States)

Author keywords

Photoreceptor; Retina; Rp2

Indexed keywords

CRE RECOMBINASE; OPSIN; PEANUT AGGLUTININ; RHODOPSIN; TRANSDUCIN;

ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DARK ADAPTATION; ELECTRORETINOGRAPHY; FEMALE; GENE; GENE EXPRESSION; GENE MUTATION; HISTOLOGY; IMMUNOBLOTTING; IMMUNOFLUORESCENCE MICROSCOPY; MALE; MICROSCOPY; MOUSE; NONHUMAN; PHOTOPIC VISION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN LOCALIZATION; RETINA PIGMENT DEGENERATION; RETINITIS PIGMENTOSA 2 GENE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TRANSMISSION ELECTRON MICROSCOPY;

PHOTORECEPTOR; RETINA; RP2;

ANIMALS; DISEASE MODELS, ANIMAL; ELECTRORETINOGRAPHY; EYE PROTEINS; GENES, X-LINKED; GENETIC DISEASES, X-LINKED; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MEMBRANE PROTEINS; MICE; OPSINS; PHOTORECEPTOR CELLS; RETINITIS PIGMENTOSA;

EID: 84879610890     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.13-12140     Document Type: Article

References (42)

1. Kennedy B, Malicki J. What drives cell morphogenesis: a look inside the vertebrate photoreceptor. Dev Dyn. 2009;238: 2115-2138.
2. Wright AF, Chakarova CF, Abd El-Aziz MM, Bhattacharya SS. Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait. Nat Rev Genet. 2010;11:273-284.
3. Nathans J, Piantanida TP, Eddy RL, Shows TB, Hogness DS. Molecular genetics of inherited variation in human color vision. Science. 1986;232:203-210.
4. Neitz M, Neitz J, Jacobs GH. Spectral tuning of pigments underlying red-green color vision. Science. 1991;252:971-974.
5. Deretic D. Post-Golgi trafficking of rhodopsin in retinal photoreceptors. Eye. 1998;12:526-530.
6. Besharse JC, Baker SA, Luby-Phelps K, Pazour GJ. Photoreceptor intersegmental transport and retinal degeneration: a conserved pathway common to motile and sensory cilia. Adv Exp Med Biol. 2003;533:157-164.
7. Besharse JC, Hollyfield JG. Renewal of normal and degenerating photoreceptor outer segments in the Ozark cave salamander. J Exp Zool. 1976;198:287-302.
8. Young RW. The renewal of photoreceptor cell outer segments. J Cell Biol. 1967;33:61-72.
9. Anand M, Khanna H. Ciliary transition zone (TZ) proteins RPGR and CEP290: role in photoreceptor cilia and degenerative diseases. Exp Opin Ther Targets. 2012;16:541-551.
10. Heckenlively JR, Yoser SL, Friedman LH, Oversier JJ. Clinical findings and common symptoms in retinitis pigmentosa. Am J Ophthalmol. 1988;105:504-511.
11. Haim M. Epidemiology of retinitis pigmentosa in Denmark. Acta Ophthalmol Scand Suppl. 2002;233:1-34.
12. Daiger SP, Bowne SJ, Sullivan LS. Perspective on genes and mutations causing retinitis pigmentosa. Arch Ophthalmol. 2007;125:151-158.
13. Breuer DK, Yashar BM, Filippova E, et al. A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa. Am J Hum Genet. 2002;70:1545-1554.
14. Churchill JD, Bowne SJ, Sullivan LS, et al. Mutations in the Xlinked retinitis pigmentosa genes RPGR and RP2 found in 8.5% of families with a provisional diagnosis of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2013;54: 1411-1416.
15. Webb TR, Parfitt DA, Gardner JC, et al. Deep intronic mutation in OFD1, identified by targeted genomic next-generation sequencing, causes a severe form of X-linked retinitis pigmentosa (RP23). Hum Mol Genet. 2012;21:3647-3654.
16. Shu X, Black GC, Rice JM, et al. RPGR mutation analysis and disease: an update. Hum Mutat. 2007;28:322-328.
17. Schwahn U, Lenzner S, Dong J, et al. Positional cloning of the gene for X-linked retinitis pigmentosa 2. Nat Genet. 1998;19: 327-332.
18. Branham K, Othman M, Brumm M, et al. Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease. Invest Ophthalmol Vis Sci. 2012;53: 8232-8237.
19. Chapple JP, Hardcastle AJ, Grayson C, Spackman LA, Willison KR, Cheetham ME. Mutations in the N-terminus of the X-linked retinitis pigmentosa protein RP2 interfere with the normal targeting of the protein to the plasma membrane. Hum Mol Genet. 2000;9:1919-1926.
20. Kuhnel K, Veltel S, Schlichting I, Wittinghofer A. Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3. Structure. 2006;14:367-378.
21. Bartolini F, Bhamidipati A, Thomas S, Schwahn U, Lewis SA, Cowan NJ. Functional overlap between retinitis pigmentosa 2 protein and the tubulin-specific chaperone cofactor C. J Biol Chem. 2002;277:14629-14634.
22. Grayson C, Bartolini F, Chapple JP, et al. Localization in the human retina of the X-linked retinitis pigmentosa protein RP2, its homologue cofactor C and the RP2 interacting protein Arl3. Hum Mol Genet. 2002;11:3065-3074.
23. Kahn RA, Volpicelli-Daley L, Bowzard B, et al. Arf family GTPases: roles in membrane traffic and microtubule dynamics. Biochem Soc Trans. 2005;33:1269-1272.
24. Schrick JJ, Vogel P, Abuin A, Hampton B, Rice DS. ADPribosylation factor-like 3 is involved in kidney and photoreceptor development. Am J Pathol. 2006;168:1288-1298.
25. Hurd T, Zhou W, Jenkins P, et al. The retinitis pigmentosa protein RP2 interacts with polycystin 2 and regulates ciliamediated vertebrate development. Hum Mol Genet. 2010;19: 4330-4344.
26. Shu X, Zeng Z, Gautier P, et al. Knock-down of the zebrafish orthologue of the retinitis pigmentosa 2 (RP2) gene results in retinal degeneration. Invest Ophthalmol Vis Sci. 2011;52: 2960-2966.
27. Patil SB, Hurd TW, Ghosh AK, Murga-Zamalloa CA, Khanna H. Functional analysis of retinitis pigmentosa 2 (RP2) protein reveals variable pathogenic potential of disease-associated missense variants. PLoS One. 2011;6:e21379.
28. Evans RJ, Schwarz N, Nagel-Wolfrum K, Wolfrum U, Hardcastle AJ, Cheetham ME. The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium. Hum Mol Genet. 2010;19:1358-1367.
29. Beltran A, Cideciyan AV, Lewin AS, et al. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa. Proc Natl Acad Sci U S A. 2012;109:2132-2137.
30. Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR. Retinal degeneration mutants in the mouse. Vis Res. 2002;42:517-525.
31. Chang B, Khanna H, Hawes N, et al. In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse. Hum Mol Genet. 2006;15: 1847-1857.
32. Sakai K, Miyazaki J. A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the cre transgene transmission. Biochem Biophys Res Commun. 1997;237:318-324.
33. LaVail MM, Matthes MT, Yasumura D, Steinberg RH. Variability in rate of cone degeneration in the retinal degeneration (rd/rd) mouse. Exp Eye Res. 1997;65:45-50.
34. Holopainen JM, Cheng CL, Molday LL, et al. Interaction and localization of the retinitis pigmentosa protein RP2 and NSF in retinal photoreceptor cells. Biochemistry. 2010;49:7439-7447.
35. Wright KJ, Baye LM, Olivier-Mason A, et al. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 2011;25:2347-2360.
36. Hong DH, Pawlyk BS, Shang J, Sandberg MA, Berson EL, Li T. A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3). Proc Natl Acad Sci U S A. 2000;97:3649-3654.
37. Thompson DA, Khan NW, Othman MI, et al. Rd9 is a naturally occurring mouse model of a common form of retinitis pigmentosa caused by mutations in RPGR-ORF15. PLoS One. 2012;7:e35865.
38. Jayasundera T, Branham KE, Othman M, et al. RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa. Arch Ophthalmol. 2010;128:915-923.
39. Schwarz N, Novoselova TV, Wait R, Hardcastle AJ, Cheetham ME. The X-linked retinitis pigmentosa protein RP2 facilitates G protein traffic. Hum Mol Genet. 2012;21:863-873.
40. Besharse JC, Hollyfield JG. Turnover of mouse photoreceptor outer segments in constant light and darkness. Invest Ophthalmol Vis Sci. 1979;18:1019-1024.
41. Nikonov SS, Brown BM, Davis JA, et al. Mouse cones require an arrestin for normal inactivation of phototransduction. Neuron. 2008;59:462-474.
42. Zhu X, Brown B, Li A, Mears AJ, Swaroop A, Craft CM. GRK1-dependent phosphorylation of S and M opsins and their binding to cone arrestin during cone phototransduction in the mouse retina. J Neurosci. 2003;23:6152-6160.