The nob2 mouse, a null mutation in Cacnalf:: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses
The nob2 mouse, a null mutation in Cacnalf:: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses
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DOI：
10.1017/s095252380623102x
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发表时间：
2006-01-01
影响因子：
1.9
通讯作者：
Gregg, RG
中科院分区：
文献类型：
--
作者：
Chang, B;Heckenlively, JR;Gregg, RG
光感受器末端谷氨酸的释放受电压依赖性钙通道(VDCC)控制。在人类中，编码阿尔法(1F)的Cacnalf基因发生突变。VDCC的亚基，是X连锁先天性静止性夜盲(CSNB2)不完全形式的基础。这些突变损害了从视杆细胞和视锥细胞到双极细胞的突触传递。在这里，我们报告了nob2(无b波2)小鼠视网膜的解剖学和功能特征，nob2是一种由Cacnalf零突变引起的自然发生的突变。毫不奇怪，在nob2小鼠中，光适应和暗适应视网膜电信号的b波都是异常的。外丛状层(OPL)结构紊乱，异位突起穿过外核层延伸至外核层，外核层起源于杆状双极细胞和水平细胞，而非超极化双极细胞。这些异位突起继续表达mGluR6，mGluR6经常与标记有突触前标记Ribeye的轮廓相关，表明可能存在异位突触形成的点。然而，突触前Ribeye阳性轮廓的形态是异常的。虽然存在锥形椎弓根，但它们的形态似乎也受到了损害。在体视网膜神经节细胞在明视条件下的视觉反应特征表明，尽管中心细胞的基本中心-周围组织保持不变，但中心细胞的动态范围有所减小；偏离中心细胞的反应没有明显变化。这些结果表明，NOB2小鼠是研究Cacnalf突变引起CSNB2的病理生理机制以及随后对视觉信息处理的影响的有价值的模型。此外，nob2鼠标代表在其中定义引导OPL中突触形成和/或维持的信号的模型系统。
Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, Mutations in the Cacnalf gene, encoding the alpha(1F). subunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina ill the nob2 (no b-wave 2) mouse, a naturally occurring Mutant Caused by a null mutation in Cacnalf. Not surprisingly, the b-waves of both the light- and dark-adapted electroretinogram are abnormal in nob2 mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the presynaptic marker Ribeye, indicating potential points of ectopic synapse formation. However, the morphology of the presynaptic Ribeye-positive profiles is abnormal. While cone pedicles are present their morphology also appears compromised. Characterizations of visual responses in retinal ganglion cells in vivo, under photopic conditions, demonstrate that ON-center cells have a reduced dynamic range, although their basic center-surround organization is retained; no alteration in the responses of OFF-center cells was evident. These results indicate that nob2 mice are a valuable model in which to explore the pathophysiological mechanisms associated with Cacnalf Mutations causing CSNB2, and the subsequent effects on Visual information processing. Further, the nob2 Mouse represents a model system in which to define the signals that guide synapse formation and/or maintenance in the OPL.