Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
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 ISI Web of Science
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
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Incerti, B.
Right arrow Articles by Ballabio, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Incerti, B.
Right arrow Articles by Ballabio, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2000, Vol. 9, No. 19 2781-2788
© 2000 Oxford University Press

Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1

Barbara Incerti1,+, Katia Cortese2, Alessandro Pizzigoni1, Enrico M. Surace1, Simona Varani1,§, Massimiliano Coppola1, Glen Jeffery3, Mathias Seeliger4, Gesine Jaissle4, Dorothy C. Bennett5, Valeria Marigo1,¶, Maria Vittoria Schiaffino1, Carlo Tacchetti2 and Andrea Ballabio1,6,¶

1Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Via Olgettina 58, I-20132 Milan, Italy, 2Department of Experimental Medicine, Anatomy Section, University of Genova, I-16132 Genova, Italy, 3University College London, Institute of Ophthalmology, London, UK, 4Retinal Electrodiagnostics Research Group, University Eye Hospital, D-72076 Tübingen, Germany, 5St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK and 6Università Vita e Salute, San Raffaele, I-20132 Milan, Italy

Ocular albinism type I (OA1) is an X-linked disorder characterized by severe reduction of visual acuity, strabismus, photophobia and nystagmus. Ophthalmologic examination reveals hypopigmentation of the retina, foveal hypoplasia and iris translucency. Microscopic examination of both retinal pigment epithelium (RPE) and skin melanocytes shows the presence of large pigment granules called giant melanosomes or macromelanosomes. In this study, we have generated and characterized Oa1-deficient mice by gene targeting (KO). The KO males are viable, fertile and phenotypically indistinguishable from the wild-type littermates. Ophthalmologic examination shows hypopigmentation of the ocular fundus in mutant animals compared with wild-type. Analysis of the retinofugal pathway reveals a reduction in the size of the uncrossed pathway, demonstrating a misrouting of the optic fibres at the chiasm, as observed in OA1 patients. Microscopic examination of the RPE shows the presence of giant melanosomes comparable with those described in OA1 patients. Ultrastructural analysis of the RPE cells, suggests that the giant melanosomes may form by abnormal growth of single melanosomes, rather than the fusion of several, shedding light on the pathogenesis of ocular albinism.

+ To whom correspondence should be addressed. Tel: +39 081 5790113; Fax: +39 081 5790919; Email: incerti@tigem.it

§ Present address: Department of Pathology, Baylor College of Medicine, Houston, TX 70030, USA

Present address: TIGEM, Via P. Castellino 11, I-80131 Naples, Italy


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
F. Giordano, C. Bonetti, E. M. Surace, V. Marigo, and G. Raposo
The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition
Hum. Mol. Genet., December 1, 2009; 18(23): 4530 - 4545.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
I. Palmisano, P. Bagnato, A. Palmigiano, G. Innamorati, G. Rotondo, D. Altimare, C. Venturi, E. V. Sviderskaya, R. Piccirillo, M. Coppola, et al.
The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells
Hum. Mol. Genet., November 15, 2008; 17(22): 3487 - 3501.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. Young, E. B. Powelson, I. E. Whitney, M. A. Raven, S. Nusinowitz, M. Jiang, L. Birnbaumer, B. E. Reese, and D. B. Farber
Involvement of OA1, an Intracellular GPCR, and G{alpha}i3, Its Binding Protein, in Melanosomal Biogenesis and Optic Pathway Formation
Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3245 - 3252.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Yamaguchi, M. Brenner, and V. J. Hearing
The Regulation of Skin Pigmentation
J. Biol. Chem., September 21, 2007; 282(38): 27557 - 27561.
[Full Text] [PDF]

Home page
 IOVSHome page
K. Cortese, F. Giordano, E. M. Surace, C. Venturi, A. Ballabio, C. Tacchetti, and V. Marigo
The Ocular Albinism Type 1 (OA1) Gene Controls Melanosome Maturation and Size
Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4358 - 4364.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
F. Vetrini, A. Auricchio, J. Du, B. Angeletti, D. E. Fisher, A. Ballabio, and V. Marigo
The Microphthalmia Transcription Factor (Mitf) Controls Expression of the Ocular Albinism Type 1 Gene: Link between Melanin Synthesis and Melanosome Biogenesis
Mol. Cell. Biol., August 1, 2004; 24(15): 6550 - 6559.
[Abstract] [Full Text] [PDF]

Home page
 Br J OphthalmolHome page
M. Preising, J.-P. O. de Laak, and B. Lorenz
Deletion in the OA1 gene in a family with congenital X linked nystagmus
Br J Ophthalmol, September 1, 2001; 85(9): 1098 - 1103.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
M. d'Addio, A. Pizzigoni, M. T. Bassi, C. Baschirotto, C. Valetti, B. Incerti, M. Clementi, M. De Luca, A. Ballabio, and M. V. Schiaffino
Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1
Hum. Mol. Genet., December 1, 2000; 9(20): 3011 - 3018.
[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.