Early synaptic defects in tulp1-/- mice.
Early synaptic defects in tulp1-/- mice.
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DOI：
10.1167/iovs.08-3190
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发表时间：
2009-07
影响因子：
4.4
通讯作者：
Hagstrom SA
中科院分区：
文献类型：
--
作者：
Grossman GH;Pauer GJ;Narendra U;Peachey NS;Hagstrom SA
光感受器特异性tubby样蛋白1（TULP 1）的突变是常染色体隐性视网膜色素变性的基础。为了研究Tulp 1在感光突触中的作用，作者检查了tulp 1 −/−小鼠的突触前和突触后结构以及视网膜功能。作者使用免疫组织化学方法检查了视网膜变性前的tulp 1 −/−小鼠，并与野生型（wt）同窝小鼠和视网膜变性10（rd 10）小鼠进行了比较，后者是另一种感光细胞变性模型，具有可比的变性率。视网膜功能的特点是使用视网膜电图。在野生型小鼠中，Tulp 1定位于光感受器突触。在tulp 1 −/−突触中，与带相关的蛋白巴松管和短笛之间的空间关系被破坏，几乎没有完整的带存在。此外，双极细胞树突发育不良。在rd 10小鼠中未观察到类似的异常。a波的前沿在tulp 1 −/−小鼠中具有正常的动力学，但在rd 10小鼠中减少了增益。与野生型小鼠相比，tulp 1 −/−小鼠的b波强度反应函数向更高的强度移动，但rd 10小鼠的b波强度反应函数没有移动。tulp 1 −/−小鼠的光感受器突触和双极细胞树突显示出异常的结构和功能。光感受器突触带的畸形可能是双极细胞树突营养不良的原因。关联的早发性，严重的感光细胞变性之前突触异常似乎代表了一个表型没有以前描述。Tulp 1不仅对感光细胞的功能和存活至关重要，而且对感光细胞突触的正常发育至关重要。
Mutations in the photoreceptor-specific tubby-like protein 1 (TULP1) underlie a form of autosomal recessive retinitis pigmentosa. To investigate the role of Tulp1 in the photoreceptor synapse, the authors examined the presynaptic and postsynaptic architecture and retinal function in tulp1−/− mice The authors used immunohistochemistry to examine tulp1−/− mice before retinal degeneration and made comparisons with wild-type (wt) littermates and retinal degeneration 10 (rd10) mice, another model of photoreceptor degeneration that has a comparable rate of degeneration. Retinal function was characterized with the use of electroretinography. In wt mice, Tulp1 is localized to the photoreceptor synapse. In the tulp1−/− synapse, the spatial relationship between the ribbon-associated proteins Bassoon and Piccolo are disrupted, and few intact ribbons are present. Furthermore, bipolar cell dendrites are stunted. Comparable abnormalities are not seen in rd10 mice. The leading edge of the a-wave had normal kinetics in tulp1−/− mice but reduced gain in rd10 mice. The b-wave intensity-response functions of tulp1−/− mice are shifted to higher intensities than in wt mice, but those of rd10 mice are not. Photoreceptor synapses and bipolar cell dendrites in tulp1−/− mice display abnormal structure and function. A malformation of the photoreceptor synaptic ribbon is likely the cause of the dystrophy in bipolar cell dendrites. The association of early-onset, severe photoreceptor degeneration preceded by synaptic abnormalities appears to represent a phenotype not previously described. Not only is Tulp1 critical for photoreceptor function and survival, it is essential for the proper development of the photoreceptor synapse.
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