Rezaie Tayebeh, Waitzman David M, Seeman Jennifer L, Kaufman Paul L, Sarfarazi Mansoor
Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Wisconsin-Madison, USA.
Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2404-10. doi: 10.1167/iovs.04-1243.
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.
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.
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.
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.
已有研究表明，视神经病相关蛋白（OPTN）基因突变与成人原发性开角型青光眼（POAG）的病因有关。鉴于人类和非人灵长类动物眼部发育及功能存在密切相似性，恒河猴被认为是研究人类视觉系统的合适模型。因此，本研究旨在克隆恒河猴中人类OPTN基因的同源基因（Rh-OPTN）并确定其基因组结构。另一个目的是建立Rh-OPTN蛋白在恒河猴眼前节、视网膜和视神经中的表达谱及组织分布。
克隆Rh-OPTN基因并确定其基因组结构。通过Northern印迹分析检测mRNA表达模式。通过免疫标记确定蛋白的细胞定位、眼部表达及组织分布。
Rh-OPTN基因有13个外显子，编码一个含571个氨基酸的蛋白。cDNA和氨基酸序列与人类OPTN的同源性均为96%。Northern印迹分析显示，在心脏、大脑、肾脏、肺、脾脏、骨骼肌和小肠中，两种不同转录本有显著表达。Rh-OPTN蛋白的细胞和组织分布与其人类和小鼠同源蛋白高度相似。
视神经病相关蛋白基因和蛋白在人类和恒河猴之间具有进化保守性。两种视神经病相关蛋白在眼部表达和组织分布上的高度相似性表明，这种非人灵长类动物是研究人类青光眼性视神经病变病理生理学和治疗方法的合适模型。
