FUNCTIONAL EFFECTS OF CARDIOMYOPATHIC MYOSIN MUTATIONS

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date5/15/954/30/96

Funding

  • National Heart, Lung, and Blood Institute

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