Myostatin自体疫苗的研究

发布时间：2018-03-23 12:28

本文选题：myostatin　切入点：基因疫苗　出处：《第四军医大学》2006年博士论文

【摘要】：Myostatin(Mstn或Ms)属于TGF-β超家族新成员，主要在骨骼肌中表达。Myostatin是骨骼肌生长发育的负调控因子，抑制myostatin的功能可明显提高骨骼肌质量。基因敲除myostatin的小鼠肌纤维有明显的增生和增粗，脂肪含量随年龄的增长而明显降低。抑制myostatin活性的蛋白如其前肽、follistatin蛋白、Act RⅡB非活性结构域蛋白高表达的转基因小鼠体重和骨骼肌质量明显提高。Myostatin蛋白酶切加工位点突变的转基因小鼠，同样显示小鼠体重增加。而抗myostatin单克隆抗体处理的杜氏肌营养不良模型小鼠(DMD)，骨骼肌质量和力量明显增加，，患病的小鼠症状明显改善，证实了myostatin作为骨骼肌生成负调节因子对成年动物也有作用，并为myostatin单克隆抗体用于临床骨骼肌发育抑制性疾病的治疗提供了依据。虽然针对myostatin蛋白的单克隆抗体在治疗肌肉相关疾病的过程中显示出了良好的效果，但是，造价的昂贵和使用上的不便限制了单克隆抗体的广泛应用，因此，由被动地接受这种抗体蛋白转向寻求针对该蛋白的主动免疫疫苗有更好的应用前景。本课题拟构建能够诱导出针对myostatin特异性中和抗体的治疗性疫
[Abstract]:Myostatin (Mstn or Ms) belongs to TGF- beta super family of new members, mainly in skeletal muscle expression of.Myostatin is a negative regulator of skeletal muscle growth, inhibit the function of myostatin can significantly improve the quality of the skeletal muscle. Myostatin gene knockout mice muscle fiber has obvious hyperplasia and thickening, fat content with age the protein decreased significantly. As the propeptide, inhibit the activity of myostatin follistatin protein, Act R II B non transgenic mice expressed high activity domain protein weight and skeletal muscle of transgenic mice and significantly improved the quality of.Myostatin protease processing site mutation, also showed that the weight gain of mice. The anti myostatin monoclonal antibody treatment for Duchenne muscular dystrophy bad mouse model (DMD), skeletal muscle mass and strength increased significantly, significantly improve the symptoms of the disease in mice, myostatin was confirmed as a negative regulator of skeletal muscle formation It also plays a role in adult animals and provides a basis for the use of myostatin monoclonal antibodies in the treatment of clinical skeletal muscle development.
Although the process of monoclonal antibody against myostatin protein in treatment of muscle disease shows a good effect, but the cost is expensive and inconvenient to use restricts the wide application of monoclonal antibody, therefore, from the passive acceptance of the antibody protein to applications seeking active immunization vaccine against this protein has better this topic intends to build can induce myostatin specific neutralizing antibodies for therapeutic vaccine

【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

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