Skip Navigation



Human Molecular Genetics Advance Access published online on April 21, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl107
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrowOA All Versions of this Article:
15/11/1847    most recent
ddl107v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Chang, B.
Right arrow Articles by Swaroop, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chang, B.
Right arrow Articles by Swaroop, A., Ph.D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org
Received March 7, 2006
Revised April 13, 2006
Accepted April 13, 2006

Article

An 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

Bo Chang 1, Hemant Khanna 2, Norman Hawes 1, David Jimeno 3, Shirley He 2, Concepcion Lillo 3, Sunil K. Parapuram 2, Hong Cheng 2, Alison Scott 2, Ron E. Hurd 1, John A. Sayer 4, Edgar A. Otto 4, Massimo Attanasio 4, John F. O'Toole 4, Genglin Jin 5, Chengchao Shou 5, Friedhelm Hildebrandt 6, David S. Williams 3, John R. Heckenlively 2, and Anand Swaroop Ph.D. 7 *

1 The Jackson Laboratory, Bar Harbor, Maine 04609, USA
2 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, USA
3 Departments of Pharmacology and Neurosciences, School of Medicine, University of California at San Diego, La Jolla, California, 92093- 0912, USA
4 Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA
5 Department of Biochemistry & Molecular Biology, Peking University School of Oncology, Beijing Institute for Cancer Research, Beijing. 100034, China
6 Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
7 Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall St., Ann Arbor, Michigan 48105, USA; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA

* To whom correspondence should be addressed.
Anand Swaroop Ph.D., E-mail: swaroop{at}umich.edu


  Abstract

Centrosome- and cilia-associated proteins play crucial roles in establishing polarity and regulating intracellular transport in post-mitotic cells. Using genetic mapping and positional candidate strategy, we have identified an in-frame deletion in a novel centrosomal protein CEP290 (also called NPHP6) leading to early-onset retinal degeneration in a newly-identified mouse mutant, rd16. We demonstrate that CEP290 localizes primarily to centrosomes of dividing cells and to the connecting cilium of retinal photoreceptors. We show that in the retina CEP290 associates with several microtubule-based transport proteins including RPGR, which is mutated in approximately 15% of patients with retinitis pigmentosa. A truncated CEP290 protein ({Delta}CEP290) is detected in the rd16 retina but in considerably reduced amounts; however, the mutant protein exhibits stronger association with specific RPGR isoform(s). Immunogold labeling studies demonstrate the redistribution of RPGR and of phototransduction proteins in the photoreceptors of rd16 retina. Our findings suggest a critical function for CEP290 in ciliary transport and provide insights into the mechanism of early-onset photoreceptor degeneration.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
S. D. Weatherbee, L. A. Niswander, and K. V. Anderson
A mouse model for Meckel syndrome reveals Mks1 is required for ciliogenesis and Hedgehog signaling
Hum. Mol. Genet., December 1, 2009; 18(23): 4565 - 4575.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
Y.-C. Hsiao, Z. J. Tong, J. E. Westfall, J. G. Ault, P. S. Page-McCaw, and R. J. Ferland
Ahi1, whose human ortholog is mutated in Joubert syndrome, is required for Rab8a localization, ciliogenesis and vesicle trafficking
Hum. Mol. Genet., October 15, 2009; 18(20): 3926 - 3941.
[Abstract] [Full Text] [PDF]

Home page
 Chem SensesHome page
P. M. Jenkins, D. P. McEwen, and J. R. Martens
Olfactory Cilia: Linking Sensory Cilia Function and Human Disease
Chem Senses, June 1, 2009; 34(5): 451 - 464.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Hildebrandt, M. Attanasio, and E. Otto
Nephronophthisis: Disease Mechanisms of a Ciliopathy
J. Am. Soc. Nephrol., January 1, 2009; 20(1): 23 - 35.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Schafer, M. Putz, S. Lienkamp, A. Ganner, A. Bergbreiter, H. Ramachandran, V. Gieloff, M. Gerner, C. Mattonet, P. G. Czarnecki, et al.
Genetic and physical interaction between the NPHP5 and NPHP6 gene products
Hum. Mol. Genet., December 1, 2008; 17(23): 3655 - 3662.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Kim, S. R. Krishnaswami, and J. G. Gleeson
CEP290 interacts with the centriolar satellite component PCM-1 and is required for Rab8 localization to the primary cilium
Hum. Mol. Genet., December 1, 2008; 17(23): 3796 - 3805.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. Okada, T. Misaka, Y. Tanaka, I. Matsumoto, K. Ishibashi, S. Sasaki, and K. Abe
Aquaporin-11 knockout mice and polycystic kidney disease animals share a common mechanism of cyst formation
FASEB J, October 1, 2008; 22(10): 3672 - 3684.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
S. Brunner, D. Colman, A. J. Travis, U. F.O. Luhmann, W. Shi, S. Feil, C. Imsand, J. Nelson, C. Grimm, T. Rulicke, et al.
Overexpression of RPGR Leads to Male Infertility in Mice Due to Defects in Flagellar Assembly
Biol Reprod, October 1, 2008; 79(4): 608 - 617.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
O. Devuyst and V. J. Arnould
Mutations in RPGRIP1L: extending the clinical spectrum of ciliopathies
Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1500 - 1503.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. P. McEwen, R. K. Koenekoop, H. Khanna, P. M. Jenkins, I. Lopez, A. Swaroop, and J. R. Martens
Hypomorphic CEP290/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons
PNAS, October 2, 2007; 104(40): 15917 - 15922.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
T. S. Aleman, A. V. Cideciyan, A. Sumaroka, S. B. Schwartz, A. J. Roman, E. A. M. Windsor, J. D. Steinberg, K. Branham, M. Othman, A. Swaroop, et al.
Inner Retinal Abnormalities in X-linked Retinitis Pigmentosa with RPGR Mutations
Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4759 - 4765.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J. Helou, E. A Otto, M. Attanasio, S. J Allen, M. A Parisi, I. Glass, B. Utsch, S. Hashmi, E. Fazzi, H. Omran, et al.
Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior Loken syndrome
J. Med. Genet., October 1, 2007; 44(10): 657 - 663.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
I. Gosens, E. van Wijk, F. F.J. Kersten, E. Krieger, B. van der Zwaag, T. Marker, S. J.F. Letteboer, S. Dusseljee, T. Peters, H. A. Spierenburg, et al.
MPP1 links the Usher protein network and the Crumbs protein complex in the retina
Hum. Mol. Genet., August 15, 2007; 16(16): 1993 - 2003.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
Q. Liu, G. Tan, N. Levenkova, T. Li, E. N. Pugh Jr., J. J. Rux, D. W. Speicher, and E. A. Pierce
The Proteome of the Mouse Photoreceptor Sensory Cilium Complex
Mol. Cell. Proteomics, August 1, 2007; 6(8): 1299 - 1317.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. E. Swiderski, D. Y. Nishimura, R. F. Mullins, M. A. Olvera, J. L. Ross, J. Huang, E. M. Stone, and V. C. Sheffield
Gene Expression Analysis of Photoreceptor Cell Loss in Bbs4-Knockout Mice Reveals an Early Stress Gene Response and Photoreceptor Cell Damage
Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3329 - 3340.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
F. Hildebrandt and W. Zhou
Nephronophthisis-Associated Ciliopathies
J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1855 - 1871.
[Abstract] [Full Text] [PDF]

Home page
 J HeredHome page
M. Menotti-Raymond, V. A. David, A. A. Schaffer, R. Stephens, D. Wells, R. Kumar-Singh, S. J. O'Brien, and K. Narfstrom
Mutation in CEP290 Discovered for Cat Model of Human Retinal Degeneration
J. Hered., May 16, 2007; (2007) esm019v1.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
K. Tory, T. Lacoste, L. Burglen, V. Moriniere, N. Boddaert, M.-A. Macher, B. Llanas, H. Nivet, A. Bensman, P. Niaudet, et al.
High NPHP1 and NPHP6 Mutation Rate in Patients with Joubert Syndrome and Nephronophthisis: Potential Epistatic Effect of NPHP6 and AHI1 Mutations in Patients with NPHP1 Mutations
J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1566 - 1575.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
N. Sugiyama and T. Yokoyama
Sustained cell proliferation of renal epithelial cells in mice with inv mutation.
Genes Cells, October 1, 2006; 11(10): 1213 - 1224.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. Fliegauf, J. Horvath, C. von Schnakenburg, H. Olbrich, D. Muller, J. Thumfart, B. Schermer, G. J. Pazour, H. P.H. Neumann, H. Zentgraf, et al.
Nephrocystin Specifically Localizes to the Transition Zone of Renal and Respiratory Cilia and Photoreceptor Connecting Cilia
J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2424 - 2433.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.