Identification of the gene and the mutation responsible for the mouse nob phenotype
Identification of the gene and the mutation responsible for the mouse nob phenotype
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DOI：
10.1167/iovs.02-0501
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发表时间：
2003-01-01
影响因子：
4.4
通讯作者：
Peachey, NS
中科院分区：
文献类型：
--
作者：
Gregg, RG;Mukhopadhyay, S;Peachey, NS
目的.现有的证据表明，自然发生的小鼠突变nob（无b波）为人类X连锁先天性静止性夜盲症（CSNB1）的完整形式提供了动物模型。本研究的目的是确定nob基因缺陷，表征相关基因的表达模式，并评估nob小鼠的视觉敏感性。定位克隆，候选基因的筛选和测序被用来确定nob基因。用北方印迹分析和原位杂交检测nyx基因的表达模式。视觉灵敏度与主动回避行为测试。nob表型是由小鼠nyx基因中85 bp的缺失引起的，该基因编码夜盲蛋白。尼克斯的表达是最丰富的视网膜，特别是在内核层。夜猫子蛋白含有富含亮氨酸的重复序列，并且侧翼为富含半胱氨酸的区域，这将其鉴定为富含小亮氨酸的蛋白聚糖家族的成员。行为学测试显示，nob小鼠的视觉灵敏度显著降低。nob小鼠是人类CSNB1的模型。这个模型将是有用的，在定义的作用，夜来香在光感受器和视网膜双极细胞之间的信号传递。
PURPOSE. The available evidence indicates that the naturally occurring mouse mutant nob (no b-wave) provides an animal model for the complete form of human X-linked congenital stationary night blindness (CSNB1). The goals of the present study were to identify the nob gene defect, to characterize the expression pattern of the involved gene, and to assess visual sensitivity in nob mice.METHODS. Positional cloning, screening of candidate genes, and sequencing were used to identify the nob gene. The expression pattern of the nyx gene was examined with Northern blot analysis and in situ hybridization. Visual sensitivity was measured with an active avoidance behavioral test.RESULTS. The nob phenotype is caused by an 85-bp deletion in the mouse nyx gene, which encodes the nyctalopin protein. Expression of nyx was most abundant in the retina and, in particular, in the inner nuclear layer. The nyctalopin protein contains I I leucine-rich repeats and is flanked by cysteine rich regions, which identifies it as a member of the small leucine rich proteoglycan family. Behavioral testing shows that nob mice have a significant decrease in visual sensitivity.CONCLUSIONS. The nob mouse is a model for human CSNB1. This model will be useful in defining the role of nyctalopin in signal transmission between photoreceptors and retinal bipolar cells.