SYNAPSES ON TRANSGENIC MUSCLE FIBERS STUDIED OVER TIME IN LIVING MICE

描述(摘自摘要)：这项工作的目的是更好地 了解影响神经的靶源成分的作用 终端维护、淘汰和增长。新开发的 将外源基因和其他分子转移到生物体内的技术 体内细胞及其修饰细胞的反应成像 时间将被用来研究神经肌肉连接。 被认为在运动终末萌发中起作用的分子的作用 通过将基因导入肌肉，通过注射，来探索 编码CNTF、BDNF、NT3、NGF和IGF-2。同情的回应， 我们将探索感觉轴突和运动轴突，以及对突触的影响 队形。肌肉中的蛋白质合成将被局部抑制，通过 在突触附近注射蓖麻毒素-60。突触前和突触后 将遵循专业化认证。这里的问题是突触的丧失 是由于最初由肌肉或肌肉提供的某些因子的去除 突触的存活是否取决于肌肉反应需要新的 蛋白质合成。乙酰胆碱受体(AChR)在心肌梗死中的作用 突触的维持将通过向突触内注入 一系列旨在降低突触后AChR的药物 综合。这些包括反义寡核苷酸，cDNA在 反义方向和编码显性负截断的cDNA AChR和43k蛋白的亚基。此外，还将努力 Made为感兴趣基因和记者开发新型腺病毒载体 基因作为一种提高转基因肌肉纤维产量的手段 就地学习。还将进行一些现场监测研究 S-层粘连蛋白等基础层蛋白缺失转基因小鼠的研究 一种研究基底膜在突触消除中作用的方法， 生长和成熟。

DESCRIPTION (from the abstract): The aim of this work is to better understand the role of target derived constituents that effect nerve terminal maintenance, elimination and growth. The newly developed techniques of transfer of exogenous genes and other molecules into living cells in vivo and the imaging of the responses of the modified cells over time will be used to study the neuromuscular junction. The role of molecules believed to play a role in motor terminal sprouting will be explored by transfecting muscles, by injection, with genes encoding CNTF, BDNF, NT3, NGF and IGF-2. The response of sympathetic, sensory and motor axons will be explored as will the effect on synapse formation. Protein synthesis will be focally inhibited in muscle by injecting ricin-60 near the synaptic site. Both pre- and postsynaptic specializations will be followed. At issue here is whether synapse loss is due to the removal of some factor initially supplied by the muscle or whether synapse survival depends on a muscle response that requires new protein synthesis. The role of the acetylcholine receptor (AChR) in synapse maintenance will be explored by injecting into the synaptic region a number of agents designed to decrease postsynaptic AChR synthesis. These include antisense oligonucleotides, cDNAs in the antisense direction and cDNAs encoding dominant negative truncations for subunits of the AChR and the 43k protein. In addition, efforts will be made to develop new adenovirus vectors for genes of interest and reporter genes as a means of increasing the yield of transfected muscle fibers to study in situ. Some in situ monitoring studies will also be conducted on transgenic mice lacking s-laminin or other basal lamina proteins as a way of investigating the role of basal lamina in synapse elimination, growth and maturation.