A versatile reporter for visualization of myelin plasticity in the genetically modified rat

摘要 髓磷脂结构是神经传导的关键调节剂，也是轴突发育的重要因素， 体内平衡近年来，一些具有开创性的观察已经消除了一个长期存在的教条， 髓磷脂是静态的、不可弯曲的结构。成像技术和标记方法的进展 髓鞘已经揭示，髓鞘可塑性发生在包裹数量和鞘长度的水平上， 纳塔尔发育、衰老和损伤后的再生。对髓鞘可塑性的观察表明， 髓鞘轴突功能的深刻作用，从而突出了对更好的工具来研究髓鞘轴突功能的迫切需要。 髓鞘形成和重塑的机制。在这里，我们提出，髓鞘的工具有限的可用性， 报道严重阻碍了我们对髓磷脂生物学的理解。阐明髓磷脂的机制 可塑性将极大地影响我们对髓鞘在神经系统中的功能以及如何在神经系统中发挥作用的理解。 髓磷脂导致衰老、损伤和疾病。我们的实验室和其他人已经开发了髓磷脂报告系统， 小鼠，但许多行为和生理研究，可以告知髓鞘功能更好 在大鼠中建模。大鼠的神经系统在行为的关键要素方面与小鼠不同， 内分泌功能、表观遗传学和神经发生。大鼠也被认为是建模的上级动物， 翻译再生疗法我们建议开发一个多功能的髓鞘膜报告系统， 大鼠能够区分新的和旧的髓鞘在神经系统与空间和时间 精度为了构建第一个大鼠髓磷脂报告基因系统，我们提出：目的1：构建大鼠髓磷脂报告基因 目的2：检测髓鞘启动子在大鼠报告系统中的特异性和效率。结果 这项研究将产生一个髓鞘标记系统，将具有独特的功能优势，为研究 髓鞘发育、髓鞘再生和老化中的髓鞘。

Abstract Myelin structure is a critical regulator of nerve conduction and an essential factor in axon development and homeostasis. In recent years, a number of seminal observations have dispelled a long-standing dogma that myelin is a static, inflexible structure. Advances in imaging techniques as well as in the methods used to label myelin have revealed that myelin plasticity occurs at the level of wrap number and sheath length during post- natal development, aging, and regeneration after injury. Observations of myelin plasticity indicate a more profound role of myelin axon function, and thereby highlight a critical need for better tools to investigate the mechanisms of myelin formation and remodeling. Here, we propose that the limited availability of tools for myelin reporting has significantly hindered our understanding of myelin biology. Illuminating the mechanisms of myelin plasticity will dramatically impact our understanding of the function of myelin in the nervous system and how myelin contributes to aging, injury, and disease. Our lab and others have developed myelin reporter systems in the mouse, but many of the behavioral and physiological studies that could inform myelin function are better modeled in the rat. The rat nervous system is unique from the mouse in terms of critical elements of behavior, endocrine function, epigenetics, and neurogenesis. Rats are also considered superior for modeling and translating regenerative therapies. We propose to develop a versatile myelin membrane reporter system in the rat capable of discriminating between new and old myelin in the nervous system with spatial and temporal precision. To generate the first myelin reporter rat system, we propose: Aim 1: Develop a rat myelin reporter system and Aim 2: Test the specificity and efficiency of myelin promoters in the rat reporter system. Results from this research will produce a myelin tagging system that will have unique functional advantages for the study of myelin development, myelin regeneration, and myelin in aging.