髓鞘是保护、支持轴突的膜性结构，在遗传和/或环境因素作用下受到损伤，可引起以多发性硬化为代表的脱髓鞘疾病，目前尚无有效治疗。斑马鱼是研究髓鞘脱失和髓鞘形成的理想动物模型，前期构建的转基因斑马鱼Tg (mbp:nfsB-egfp)可在甲硝唑诱导下发生特异性髓鞘脱失，基因芯片表达谱分析发现白细胞介素7受体（il7r）表达下调。本项目在此基础上，以斑马鱼为模型深入研究il7r在髓鞘脱失与形成的作用。研究工作包括四部分：第一，成体鱼髓鞘脱失的影像学和运动功能改变以及il7r在少突胶质细胞的表达；第二，il7r在特异性髓鞘脱失中的作用途径与机制；第三，通过对胚胎斑马鱼敲减il7r基因研究其在髓鞘形成的作用；第四，构建il7r基因敲除的斑马鱼突变体，探究il7r与少突胶质细胞分化的关系。上述工作将进一步阐明髓鞘脱失的发病机制，并为开发以il7r为靶点治疗多发性硬化等脱髓鞘疾病提供理论依据。

The myelin sheath is the membrane structure protecting, supporting and nourishing axons. Demyelinating diseases are a variety of diseases in which the neuronal myelin sheath is damaged due to genetic, environmental factors or unknown factors. The myelin structure, myelin synthesis and gene expression are highly conserved between zebrafish and mammals. Therefore, zebrafish is an ideal model to study the demyelination and myelination. In the previous study, we generated a heritable and stable transgenic line Tg (mbp:nfsB-egfp). Treatment of Tg (mbp:nfsB-egfp) larvae with metronidazole (Mtz) resulted in the selective ablation of oligodendrocytes and led to demyelination. Array analysis showed that interleukin 7 receptor (il7r) gene was strongly downregulated during this demyelination. However, gaps still remain regarding the role of il7r during demyelination. Our aim is to test the hypothesis that il7r regulates the demyelination or myelination. Four sub aims will be undertaken: (1) the expression of il7r, morphology, imaging and behaviors will be tested on an adult demyelinating model; (2) the expression of molecules or genes in il7r related pathways will be tested to characterize the mechanisms of il7r down-regulation; (3) the effects of il7r in embryonic myelination will be studied by the targeted knockdown of il7r with morpholino oligonucleotides and (4) il7r knockout mutant zebrafish will be generated to investigate the role of il7r on the differentiation of oligodendrocytes. The studies proposed here will contribute to the comprehensive understanding of il7r in demyelination and myelination and will help develop therapies for il7r-based treatment of demyelinating diseases in humans.