Anatomic variations in muscle gene expression

肌肉基因表达的解剖学变异

• 批准号: 7050111
• 负责人: PETER B. KANG
• 金额: $ 16.81万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-06 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7050111
• 关键词: children; clinical research; dystrophin; gene expression profiling; gene mutation; human tissue; laboratory mouse; muscle proteins; muscular dystrophy; myotubes; protein localization; protein protein interaction; tissue /cell culture

DESCRIPTION (provided by applicant): The candidate is a pediatric neurologist specializing in neuromuscular diseases who wishes to acquire the training needed to become an independent physician scientist. He plans to study the pathophysiology of the muscular dystrophies and take courses in genomics and biochemistry. The environment consists of mentors, colleagues, and collaborators who have the expertise needed for such training, as well as a well equipped laboratory. The candidate hopes to use genomic techniques to correlate animal models to human disease and identify targets for the pharmacologic treatment of neuromuscular diseases. The research project addresses the selective involvement of different skeletal muscles in the muscular dystrophies. This finding has long remained unexplained, and cannot be attributed solely to anatomic or histologic features. Gene expression techniques and divergent phenotypes among the dysferlinopathies provide a new means of approaching this question. The overall hypothesis is that differences between muscles at the molecular level are related to their varying responses to genetic insults; these differences will be examined in both normal and dysferlin-deficient muscle. Aim 1 is to create a molecular map of human skeletal muscle groups using gene expression analysis. The resulting data will be compared to that already available for mouse muscles; the interspecies correlation will assist in the interpretation of therapeutic trials in mice. Aim 2 is to identify gene expression differences between muscle specimens obtained from individuals displaying two different phenotypes of dysferlin deficiency, limb girdle muscular dystrophy 2B and Miyoshi myopathy. Aim 3 is to perform analyses on the protein products of genes identified in Aims 1 and 2 to determine associations with dysferlin and dystrophin. Proteins that are determined to interact with dysferlin and dystrophin may be potentially targets for pharmacologic therapies.

描述（由申请人提供）：