Models Core

模型核心（核心C）将为项目1和2提供四个基本支持要素。一是 Models Core将负责繁殖和维持mdx小鼠，以进行两项研究中所述的实验。 项目1和2。Duchenne型肌营养不良症mdx小鼠模型是验证基因的必要条件 如该U54申请中所提出的治疗效果。其次，模型核心将提供所有 mdx小鼠中基因功能的生理学评估。这些包括offeree和偏心 趾长伸肌的收缩测量。这些措施被认为是 在这个FDA接受的DMD动物模型中受损，因此将为每种疾病提供重要标准。 项目旨在证明肌肉功能改善的生理学显著临床措施。 这种验证对于证明疗效至关重要。第三，核心将负责住房和 在这两个项目中描述的实验中照顾恒河猴。手术的非人灵长类动物 对于评价较大动物种属的免疫学、分布和疗效至关重要， FDA。第四，Core将在mdx和mdx中执行和优化区域血管输送方案。 小鼠和恒河猴，以通过rAAV介导的递送人微肌养蛋白和CT GAINAc转移酶 通过股动脉将基因输送到下肢的肌肉。这其中所涉及的技能 传递系统最好通过重复的性能获得。在核心中提供这种技术是 这对两个项目实现一致性至关重要，对转基因的一致分布至关重要。 在目标肌肉（腓肠肌）内。

The Models Core (Core C) will provide four essential support elements for Projects 1 and 2. First, the Models Core will be responsible for breeding and maintaining mdx mice for experiments described in both projects 1 and 2. The mdx mouse model for Duchenne muscular dystrophy is essential for verifying gene therapeutic efficacy as proposed in this U54 application. Second, the Models Core will provide all physiological assessments of gene function in the mdx mouse. These consist offeree and eccentric contraction measurements of the extensor digitorum longus muscle. These measures are known to be impaired in this FDA accepted animal model for DMD, and thus will provide important criteria for each Project to demonstrate a physiologically significant clinical measure of improvement in muscle function. Such validation is critical for demonstrating efficacy. Third, the core will be responsible for the housing and care of rhesus macaque monkeys for experiments described in both projects. Non-human primate animals are essential to evaluate the immunology, distribution, and efficacy in a larger animal species for review by the FDA. Fourth, the Core will perform and optimize regional vascular delivery protocols, in both the mdx mouse and rhesus macaque, to deliver human micro-dystrophin and CT GAINAc transferase via rAAVSmediated gene delivery to the muscles of the lower limb via the femoral artery. The skills involved in this delivery system are best acquired by repeated performance. Providing this technique in the Core is essential to achieve uniformity for both projects, and is essential for consistent distribution of transgenes within the targeted muscle (gastrocnemius).