MICE LACKING SYNAPTOPHYSIN REPRODUCE AND FORM TYPICAL SYNAPTIC VESICLES
MICE LACKING SYNAPTOPHYSIN REPRODUCE AND FORM TYPICAL SYNAPTIC VESICLES
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DOI：
10.1007/s004410050493
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发表时间：
1995-12-01
影响因子：
3.6
通讯作者：
LEUBE, RE
中科院分区：
文献类型：
--
作者：
ESHKIND, LG;LEUBE, RE
突触素是神经内分泌细胞中神经元和类似囊泡的小（30-50 nm）电子传递囊泡的小（30-50 nm）电子传递囊泡的主要整合膜蛋白之一。由于其表达与这些囊泡类型的发生紧密相关，因此我们在胚胎干细胞中突变了X染色体的突触素基因，以生成突触素缺陷型小鼠的产生这种囊泡在体内。缺乏突触素蛋白的小鼠的行为和外观与它们的窝和生殖能力没有区别，与正常小鼠相当。此外，在其他几种神经元多肽的表达或突触素同工型的mRNA水平，密切相关的神经元突触蛋白/突触possiniii和无处不在的幽灵蛋白中，没有明显的补偿性变化。几个神经元和神经内分泌组织的免疫荧光显微镜表明，在没有突触素蛋白的情况下保持了整体组织结构，并且其他突触囊泡成分的分布尚未明显影响。在电子显微镜制剂中，在突触缺陷型小鼠的突触区域中可见大量直径为39.9 nm和电子透射内部的囊泡；这些囊泡可以用抗突触囊泡蛋白的抗体标记，例如Synaptobrevin 2。
Synaptophysin is one of the major integral membrane proteins of the small (30-50 nm diameter) electron-translucent transmitter-containing vesicles in neurons and of similar vesicles in neuroendocrine cells. Since its expression is tightly linked to the occurrence of these vesicle types, we mutated the X-chromosomally located synaptophysin gene in embryonic stem cells for the generation of synaptophysin-deficient mice in order to study the consequence of synaptophysin ablation for the formation and function of such vesicles in vivo. The behavior and appearance of mice lacking synaptophysin was indistinguishable from that of their litter mates and reproductive capacity was comparable to normal mice. Furthermore, no drastic compensatory changes were noted in the expression of several other neuronal polypeptides or in the mRNA levels of synaptophysin isoforms, the closely related neuronal synaptoporin/synaptophysinII, and the ubiquitous pantophysin. Immunofluorescence microscopy of several neuronal and neuroendocrine tissues showed that overall tissue architecture was maintained in the absence of synaptophysin, and that the distribution of other synaptic vesicle components was not visibly affected. In electron-microscopic preparations, large numbers of vesicles with a diameter of 39.9 nm and an electron-translucent interior were seen in synaptic regions of synaptophysin-deficient mice; these vesicles could be labeled by antibodies against synaptic vesicle proteins, such as synaptobrevin 2.