FUNCTIONAL EFFECTS OF CARDIOMYOPATHIC MYOSIN MUTATIONS

心肌病肌球蛋白突变的功能影响

• 批准号: 2211265
• 负责人: EDWARD B LANKFORD
• 金额: $ 8.76万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2211265
• 关键词: biopsy; gene mutation; human subject; mutant; myocardium disorder; myofibrils; myosins; myotubes; striated muscles; tissue /cell culture

DESCRIPTION: This project is aimed at defining the functional deficits resulting from cardiac myosin mutations that cause hypertrophic cardiomyopathy (HCM). Experiments will be carried out on human slow skeletal muscle fibers obtained from biopsies from normal and HCM patients, as well as on cultured quail myotubes transfected with human cardiac myosin heavy chains. The central hypothesis is that the mutant myosin in HCM has impaired function. Dr. Lankford will use molecular techniques to create mutant human myosin heavy chain constructs that will be expressed in quail myogenic cell cultures. Some of the mutant myosins to be constructed will resemble the naturally occurring mutant myosins found in patients with HCM, while others will have different mutations. Mechanical studies will be performed on isolated myotubes from these cultures to allow quantification of the performance of mutated myosin. The applicant will also study skeletal muscle biopsies from humans with HCM. These studies in these two different systems will allow an increased understanding of the process of force generation by actin- myosin interaction, and the structure/function relationship in the myosin heavy chain. The studies will be performed in the laboratory of Dr. Lee Sweeney, an assistant professor, with consultation with Dr. Judith L. Swain, an internationally recognized leader in the field of muscle biology.

描述： 该项目旨在定义由 引起肥厚性心肌病（HCM）的心脏肌球蛋白突变。 实验将在人类慢骨骼肌纤维上进行 从正常患者和HCM患者的活检中获得 培养的鹌鹑肌管被人类心脏肌球蛋白重f 链。 中心假设是HCM中的突变体肌球蛋白具有 功能受损。兰克福德博士将使用分子技术来创建 突变的人肌球蛋白重链结构将在 鹌鹑肌原细胞培养物。 一些突变的肌球蛋白是 构造将类似于发现的天然突变体肌球蛋白 在HCM患者中，而其他患者则具有不同的突变。 机械研究将在这些孤立的肌管上进行 培养物可以量化突变的肌球蛋白的性能。 申请人还将研究来自人类的骨骼肌活检 HCM。 这些在这两个不同系统中的研究将允许 通过肌动蛋白对产生力产生过程的了解增加 肌球蛋白的相互作用以及结构/功能关系 肌球蛋白重链。 研究将在实验室进行 助理教授Lee Sweeney博士与博士咨询。 朱迪思·斯温（Judith L. Swain），国际公认的领导人 肌肉生物学。