Muscle Function and Animal Handling Core

核心C是动物处理和功能分析核心。这个设施位于芝加哥大学。该核心设施将直接接收来自项目的动物，包括巴尔的摩和辛辛那提的项目。动物将使用SHIRPA协议的一个子集进行功能分析，该协议是为体内肌肉功能分析而开发的。随后，这些小鼠的材料将提供给Core B（组织病理学Core）进行定量和定性分析。肌萎缩症研究中一个长期存在的假设是，膜完整性的丧失是导致骨骼肌纤维变性导致疾病的主要原因。病变骨骼肌中肌纤维的变性和坏死诱导邻近肌纤维、成纤维细胞和炎症细胞释放细胞因子、趋化因子和生长因子，这些细胞浸润到组织中以清除细胞碎片。TGFB和相关TGPB超家族成员（如肌生长抑制素）的释放参与了改变MD中肌纤维生长、再生和纤维化的旁分泌环境。肌萎缩症的遗传模型在解剖导致该疾病和改变其反应的分子效应物方面具有重要意义。该核心将提供这些模型的功能分析，并为病理分析提供材料，以解剖TGFB超家族在编程疾病和纤维化中的信号传导关系

Core C is the Animal Handling and Functional Analysis Core. This facility is located at the University of Chicago. This Core facility will receive animals directly from the Projects, including the Projects in Baltimore and Cincinnati. Animals will undergo functional analysis using a subset of the SHIRPA protocols that were developed for analysis of in vivo muscle function. Following this, materials from these mice will be made available to Core B, the Histopathology Core, for quantitative and qualitative analysis. A longstanding hypothesis in muscular dystrophy research is that loss of membrane integrity is a primary event leading to the degeneration of skeletal muscle fibers resulting in disease. Degeneration and necrosis of myofibers in diseased skeletal muscle induces release of cytokines, chemokines, and growth factors from neighboring myofibers, fibroblasts, and inflammatory cells that infiltrate into the tissue to remove cellular debris. Release of TGFB and related TGPB superfamily members, such as myostatin, is involved in this paracrine milieu that alters both myofiber growth, regeneration, and fibrosis in MD. Genetic models of muscular dystrophy have been of great importance in dissecting the molecular effectors that lead to this disease and alter its response. This core will provide functional analysis of these models and provide materials for pathological analysis to dissect signaling relationships in the TGFB super family in programming disease and fibrosis in muscular dystrophy. All three projects in the PPG will extensively use genetically modified mouse models to isolate single gene function to uncover new therapeutic opportunities. The Projects will also test new and existing drug to modify these pathways including soluble receptor and signaling inhibitors. This Core will analyze the results of these manipulations. The Core is an essential component for the success of the PPG.