FUNCTIONAL EFFECTS OF CARDIOMYOPATHIC MYOSIN MUTATIONS

产品说明： 该项目旨在确定由以下原因造成的功能缺陷： 心肌肌球蛋白突变导致肥厚型心肌病（HCM）。 实验将在人类慢速骨骼肌纤维上进行 从正常和HCM患者的活检中获得，以及 转染人心肌肌球蛋白重链的鹌鹑肌管 店 核心假设是HCM中的突变肌球蛋白具有 功能受损。兰克福德博士将利用分子技术 突变的人肌球蛋白重链构建体，其将在 鹌鹑生肌细胞培养物。 一些突变的肌球蛋白 构建的肌球蛋白类似于发现的天然突变肌球蛋白， 在HCM患者中，而其他人会有不同的突变。 机械研究将进行分离肌管从这些 培养物以允许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。 在这两个不同系统中的这些研究将允许 增加对肌动蛋白产生力的过程的理解- 肌球蛋白的相互作用，和结构/功能关系， 肌球蛋白重链 研究将在以下实验室进行： 助理教授Lee Sweeney博士与Dr. 朱迪思湖Swain是国际公认的 肌肉生物学

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.