MOLECULAR MECHANISM OF SCHWANN CELL MYELINATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 NCMR的资源对于检查沿着有髓鞘轴突的三维运输是非常宝贵的。 在脊椎动物神经系统中，髓磷脂是一种多层膜绝缘体，它包围着轴突并促进快速的神经通讯。 我们正在研究在CNS神经胶质中表达P0而不是PLP的基因工程小鼠。 令人惊讶的是，在PLP的情况下，P0提供了一个良好的有序结构的小鼠CNS髓鞘，但有序的结构类似于在哺乳动物外周神经系统（PNS）髓鞘中发现的，其中P0是主要的结构蛋白。 因此，PLP和PO的存在或不存在似乎定义了髓鞘的有序结构。 然而，这些小鼠的寿命减少了50%，可能是因为轴突变性。 在CNS髓鞘中具有等量P0和PLP的小鼠具有正常的寿命并且没有轴突变性。我们用电子显微镜来阐明轴突变性前有髓鞘轴突的变化。初步研究表明，在轴突运输或附近的朗维尔节点的改变。我们怀疑，轴突细胞骨架的三维组织在节点区域改变。这一假设正在测试与高压显微镜和厚切片常规使用的NCMIR。 三维重建是从倾斜系列产生的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The resources at the NCMIR are invaluable for examining the three-dimensional transport along myelinated axons. In the vertebrate nervous system, myelin is a multilayer membrane insulation that surrounds axons and promotes rapid nerve communication. We are investigating genetically engineered mice that express P0 instead of PLP in CNS glia. Surprisingly, in the absence of PLP, P0 provided a well ordered structure to mouse CNS myelin, but the ordered structure resembled that found in mammalian peripheral nervous system (PNS) myelin where P0 is the major structural protein. Thus, the presence or absence of PLP and P0 appears to define the ordered structure of myelin. However, the lifespan of these mice was reduced by 50%, presumably because of the axonal degeneration. Mice with equal amounts of P0 and PLP in CNS myelin had normal life spans and no axonal degeneration. We are using electron microscopy to elucidate changes in the myelinated axon that precede axonal degeneration. Preliminary studies indicate alterations in the axonal transport at or near nodes of Ranvier. We suspect that the 3-dimentional organization of axonal cytoskeleton is altered in nodal regions. This hypothesis is being tested with the high voltage microscope and thick sections routinely used at the NCMIR. Three-dimensional reconstructions are being generated from tilt series.