Isolation of congenital stationary night blindness genes

描述（由申请人提供）：在适应黑暗的条件下，谷氨酸在杆状和锥状光感受器的末端以最大速率释放。外节段光色素吸收光的最终结果是使光感受器超极化并降低谷氨酸释放的速率。这种减少是由视网膜的二级神经元，水平细胞和双极细胞上的谷氨酸受体检测到的。由于水平和超极化的双极细胞都使用离子型谷氨酸受体，这两种细胞类型在黑暗中都保持去极化状态，并在光照下保持超极化状态。相比之下，去极化双极细胞（DBCs）含有代谢性谷氨酸受体mGluR6。由于一个不完全定义的信号转导级联，dbc在黑暗中是超极化的，在光的响应下是去极化的。迄今为止，仅鉴定了该过程的两个关键蛋白，mGluR6和Galpha/0，并且DBC信号转导过程的大部分仍有待阐明。夜乐素是一种新发现的蛋白，似乎在DBC信号转导中起关键作用。众所周知，夜猫素突变是人类csnb1和小鼠nob突变的基础，这两种疾病都以缺乏DBC功能为特征。本项目的总体目标是确定夜茄碱在DBC活性中的功能作用。这个问题将在几个互补的实验中解决。有三个具体目标；1)确定夜酞肽蛋白的细胞和亚细胞位置，2)确定nob小鼠DBCs的电生理特性，3)确定与夜酞肽相互作用的蛋白。在这个项目完成后，我们希望能对夜茄碱在DBC信号转导中的作用有一个透彻的了解，并确定参与这一重要过程的其他蛋白质。

DESCRIPTION (provided by applicant): Under dark-adapted conditions, glutamate is released at a maximal rate at the terminals of rod and cone photoreceptors. The net result of light absorption by outer segment photopigments is to hyperpolarize the photoreceptor and to reduce the rate of glutamate release. This reduction, is detected by glutamate receptors on the second order neurons of the retina, the horizontal and bipolar cells. As ionotropic glutamate receptors are used by horizontal and hyperpolarizing bipolar cells, both of these cell types are maintained in a depolarized state in darkness and are hyperpolarized in response to light. In comparison, depolarizing bipolar cells (DBCs) incorporate a metabotropic glutamate receptor, mGluR6. As a result of an incompletely defined signal transduction cascade, DBCs are hyperpolarized in darkness and depolarize in response to light. To date, only two key proteins of this process have been identified, mGluR6 and Galpha/0, and much of the DBC signal transduction process remains to be elucidated. Nyctalopin is a newly identified protein that appears to play some key role in DBC signal transduction. Mutations in nyctalopin are known to underlie human CSNB 1 and the nob mutant mouse, and both disorders are characterized by a lack of DBC function. The overall goal of the present project is to define the functional role of nyctalopin in DBC activity. This question will be addressed in several complementary experiments. There are three specific aims; 1) Determine the cellular and subcellular location of the nyctalopin protein, 2) Determine the electrophysiological properties of DBCs from nob mice, and 3) Identify proteins that interact with nyctalopin. At the completion of this project, we expect to have a thorough understanding of the role that nyctalopin plays in DBC signal transduction, and to have identified additional proteins involved in this important process.