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(Investigative Ophthalmology and Visual Science. 2005;46:2404-2410.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-1243

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Molecular Cloning and Expression Profiling of Optineurin in the Rhesus Monkey

Tayebeh Rezaie,1 David M. Waitzman,2 Jennifer L. Seeman,3 Paul L. Kaufman,3,4 and Mansoor Sarfarazi1

1From the Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, and the 2Department of Neurology, University of Connecticut Health Center, Farmington, Connecticut; the 3Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin; and 4The Wisconsin National Primate Research Center, Madison, Wisconsin.

PURPOSE. It has been shown that mutations in the optineurin (OPTN) gene are involved in the etiology of adult-onset primary open-angle glaucoma (POAG). In view of close similarities between human and nonhuman primate ocular development and function, the rhesus monkey is considered a suitable model for human visual system research. Therefore, this study was conducted to clone the orthologue of the human OPTN gene in the rhesus monkey (Rh-OPTN) and to determine its genomic organization. A further purpose was to establish Rh-OPTN protein expression profiles and tissue distribution in the rhesus anterior segment, retina, and optic nerve.

METHODS. The Rh-OPTN gene was cloned and its genomic structure determined. The mRNA expression pattern was examined by Northern blot analysis. The protein’s cellular localization, ocular expression, and tissue distribution were established by immunolabeling.

RESULTS. The Rh-OPTN gene has 13 exons and encodes for a 571-amino-acid protein. Both cDNA and amino acid sequences are 96% identical with the human OPTN. Northern blot analysis revealed prominent expression of two different transcripts in heart, brain, kidney, lung, spleen, skeletal muscle, and small intestine. Cellular and tissue distribution of Rh-OPTN protein were highly similar to its human and mouse homologous proteins.

CONCLUSIONS. The optineurin gene and protein are evolutionary conserved between humans and the rhesus monkey. High similarity of ocular expression and tissue distribution between the two optineurin proteins suggests that this nonhuman primate is a suitable model for the pathophysiology and treatment of human glaucomatous optic neuropathy.





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Am. J. Pathol.Home page
B.-C. Park, X. Shen, M. Samaraweera, and B. Y.J.T. Yue
Studies of Optineurin, a Glaucoma Gene: Golgi Fragmentation and Cell Death from Overexpression of Wild-Type and Mutant Optineurin in Two Ocular Cell Types
Am. J. Pathol., December 1, 2006; 169(6): 1976 - 1989.
[Abstract] [Full Text] [PDF]




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