A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration
A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration
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DOI：
10.1093/hmg/ddr080
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发表时间：
2011-05-15
影响因子：
3.5
通讯作者：
Ayyagari, Radha
中科院分区：
文献类型：
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作者：
Chavali, Venkata R. M.;Khan, Naheed W.;Ayyagari, Radha
晚发性视网膜黄斑变性（L-ORD）是由CTRP 5/C1 QTNF 5蛋白中的单个错义突变（S163 R）引起的常染色体显性遗传疾病。L-ORD的早期表型特征包括：暗适应异常、夜盲症和周边黄斑区的玻璃疣沉积。除了眼后段异常外，这些患者还出现异常长的前透镜悬韧带。在生命的第六个十年，视杆和视锥功能下降，伴有视网膜电图（ERG）异常。一些患者还发展脉络膜新生血管和青光眼。为了了解视网膜营养不良中涉及的疾病病理学和机制，我们产生了在小鼠Ctrp 5/C1 QTNF 5基因中携带疾病相关突变的敲入（Ctrp 5（+/-））小鼠模型。这些小鼠发展较慢的rod-b波恢复，与早期暗适应异常、超自发荧光斑点的积累、视网膜色素上皮异常、玻璃疣、布鲁赫膜异常、光感受器丧失和视网膜血管渗漏一致。Ctrp 5（+/-）小鼠具有年龄相关性黄斑变性的大部分病理特征，是独特的，可以作为理解迟发性视网膜变性的分子病理学和评估治疗的有价值的模型。
Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5(+/-)) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5(+/-) mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies.