Evaluation of the rhodopsin knockout mouse as a model of pure cone function.
Evaluation of the rhodopsin knockout mouse as a model of pure cone function.
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DOI：
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发表时间：
2001-02
影响因子：
4.4
通讯作者：
G. Jaissle;C. May;Jens Reinhard;Konrad Kohler;Sascha Fauser;Elke Lütjen – Drecoll;E. Zrenner;Mathias W. Seeliger
中科院分区：
文献类型：
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作者：
G. Jaissle;C. May;Jens Reinhard;Konrad Kohler;Sascha Fauser;Elke Lütjen – Drecoll;E. Zrenner;Mathias W. Seeliger
目的确定视紫红质敲除小鼠（Rho(-/-)）视网膜功能已经充分发育但锥体变性尚未严重的时间窗口，从而代表全锥体视网膜。方法对14只纯合子Rho（-/-）小鼠和8只C57Bl/6对照小鼠进行视网膜电图（ERGs）检测。同样的个体每7天进行一次测试，从出生后第14天开始。ERG方案包括光性和暗性条件下的闪光和闪烁刺激。在相当年龄的动物中观察视网膜和脉络膜形态。结果功能上，Rho（-/-）小鼠和对照动物的发育阶段持续到出生后第3周（PW）。在PW4 - 6期间，Rho（-/-）小鼠的ERG参数呈平稳状态，锥体反应正常甚至超正常，杆状反应完全消失。在PW7时，出现了明显的退化，其进展使得PW13时没有留下ERG信号，而对照眼仍有正常的ERG反应。显微镜下，视锥变性与功能改变平行，大约在PW6开始，在PW13几乎完全，而视网膜色素上皮（RPE）和脉络膜未显示任何异常。结论从PW4到6，Rho（-/-）小鼠锥体功能正常，杆状细胞功能缺失。尽管缺失了杆状体外段（OS），但视网膜、RPE和脉络膜的结构保持不变。因此，Rho（-/-）小鼠可以在这个年龄段作为纯锥体功能的模型。这种模型对于评估杆状体-锥体相互作用和解剖杆状体-锥体介导的体内信号通路特别有用。
PURPOSE To determine a time window in the rhodopsin knockout (Rho(-/-)) mouse during which retinal function is already sufficiently developed but cone degeneration is not yet substantial, thus representing an all-cone retina. METHODS Electroretinograms (ERGs) were obtained from 14 homozygous Rho(-/-) mice and eight C57Bl/6 control mice. The same individuals were tested every 7 days, beginning as early as postnatal day (P)14. The ERG protocols included flash and flicker stimuli, both under photopic and scotopic conditions. Retinal and choroidal morphology was observed in animals of comparable age. RESULTS Functionally, the developmental phase lasted until postnatal week (PW)3 in both the Rho(-/-) mice and the control animals. During PW4 to 6, the Rho(-/-) mice showed a plateau in ERG parameters with normal or even supernormal cone responses and complete absence of rod contributions. At PW7, there was a marked onset of degeneration, which progressed so that no ERG signals were left at PW13, when the control eyes still had normal ERG responses. Microscopically, cone degeneration paralleled the functional changes, beginning at approximately PW6 and almost complete at PW13, whereas retinal pigment epithelium (RPE) and choroid did not show any abnormalities. CONCLUSIONS From PW4 to 6, Rho(-/-) mice appear to have normal cone and no rod function. Despite the missing rod outer segment (OS), the structure of retina, RPE, and choroid remained unchanged. Therefore, the Rho(-/-) mice can serve during this age period as a model for pure cone function. Such a model is particularly useful to evaluate rod-cone interaction and to dissect rod- from cone-mediated signaling pathways in vivo.