Center for Neuroscience, University of California Davis, Davis, CA 95616, USA.
Department of Cell Biology and Human Anatomy, University of California Davis, Davis, CA 95616, USA; EyePod Small Animal Ocular Imaging Laboratory, University of California Davis, Davis, CA 95616, USA; Department of Ophthalmology & Vision Science, University of California Davis, Davis, CA 95616, USA.
Exp Eye Res. 2018 Jun;171:111-118. doi: 10.1016/j.exer.2018.02.024. Epub 2018 Mar 5.
Rods and cones mediate visual perception over 9 log units of light intensities, with both photoreceptor types contributing to a middle 3-log unit range that comprises most night-time conditions. Rod function in this mesopic range has been difficult to isolate and study in vivo because of the paucity of mutants that abolish cone signaling without causing photoreceptor degeneration. Here we describe a novel Gnat2 knockout mouse line (Gnat2) ideal for dissecting rod and cone function. In this line, loss of Gnat2 expression abolished cone phototransduction, yet there was no loss of cones, disruption of the photoreceptor mosaic, nor change in general retinal morphology up to at least 9 months of age. Retinal microglia and Müller glia, which are highly sensitive to neuronal pathophysiology, were distributed normally with morphologies indistinguishable between Gnat2 and wildtype adult mice. ERG recordings demonstrated complete loss of cone-driven a-waves in Gnat2 mice; comparison to WT controls revealed that rods of both strains continue to function at light intensities exceeding 10 photoisomerizations rod s. We conclude that the Gnat2 mouse is a preferred model for functional studies of rod pathways in the retina when degeneration could be an experimental confound.
视杆细胞和视锥细胞介导的视觉感知范围跨越 9 个对数单位的光强度，这两种光感受器类型都有助于中间 3 个对数单位的范围，包括大多数夜间条件。由于缺乏能够消除视锥信号而不引起光感受器变性的突变体，因此在体内很难分离和研究这个中视范围内的视杆功能。在这里，我们描述了一种新型的 Gnat2 敲除小鼠品系（Gnat2），非常适合剖析视杆和视锥的功能。在这条品系中，Gnat2 表达的缺失消除了视锥光转导，但没有丧失视锥、破坏光感受器镶嵌、也没有改变一般视网膜形态，至少在 9 个月大时仍然如此。对神经元病理生理学高度敏感的视网膜小胶质细胞和 Müller 胶质细胞分布正常，其形态在 Gnat2 和野生型成年小鼠之间没有区别。ERG 记录显示 Gnat2 小鼠中完全丧失了视锥驱动的 a 波；与 WT 对照的比较表明，两种品系的视杆在超过 10 个光异构化视杆 s 的光强度下仍继续发挥作用。我们得出结论，当退行性变可能成为实验混杂因素时，Gnat2 小鼠是研究视网膜中视杆通路功能的首选模型。
