FUNCTIONAL EFFECTS OF CARDIOMYOPATHIC MYOSIN MUTATIONS

心肌病肌球蛋白突变的功能影响

• 批准号: 6167275
• 负责人: EDWARD B LANKFORD
• 金额: $ 8.84万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 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 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6167275
• 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.

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