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Mutations of Cardiac Troponin I cause Restrictive Cardiomyopathy; is cTnI N-terminal deletion an effective rescuing approach ?
Title
Mutations of Cardiac Troponin I cause Restrictive Cardiomyopathy; is cTnI N-terminal deletion an effective rescuing approach ?.
Creator
Getfield, Cecile A., Nan, Changlong, Graduate College, Huang, Xupei
Abstract/Description
Cardiomyopathy is a disorder which affects the heart muscle and causes varied physiological dysfunctions. Restrictive cardiomyopathy RCM is a cardiac muscle disorder in which the left ventricle becomes stiff, due to relaxation impairment. Mutations of the sarcomeric protein cardiac troponin I cTnI gene is found to cause idiopathic RCM. These mutations of cTnI are located in the C-terminus and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical...
Show moreCardiomyopathy is a disorder which affects the heart muscle and causes varied physiological dysfunctions. Restrictive cardiomyopathy RCM is a cardiac muscle disorder in which the left ventricle becomes stiff, due to relaxation impairment. Mutations of the sarcomeric protein cardiac troponin I cTnI gene is found to cause idiopathic RCM. These mutations of cTnI are located in the C-terminus and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical patients with RCM have been generated by expressing the mutant cTnI in the heart. RCM-linked mutations increase cardiac myofilament Ca2 sensitivity and promote diastolic dysfunction in the heart. In our laboratory, we have generated double transgenic mice cTnI R193H/ND/KO by crossing the cTnI R193H mice with transgenic cTnI-N terminal truncated mice cTnI-ND. Previous studies using the double transgenic mice showed that ventricular relaxation is enhanced in these mice. This study’s aim is to investigate whether or not the cardiac troponin I N-terminal deletion cTnI-ND corrects the debilitating effects caused by the cTnI R193H high expression in the heart. In doing so, we have first confirmed the genetypes of each experimental group. Echocardiography measurements have been performed on the animals at age 19-21 days. Our data indicate that cTnI R193H/KO showed a significant diastolic dysfunction, whereas the cardiac function in double transgenic mice did not show any difference compared to that in the wild type group, suggesting a functional correction by cTnI-ND in RCM phenotype.


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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00005147
Format
Document (PDF)
cTnI N-Terminal deletion: an agent for rescuing restrictive cardiomyopathy, a disease caused by mutations of Cardiac Troponin I
Title
cTnI N-Terminal deletion: an agent for rescuing restrictive cardiomyopathy, a disease caused by mutations of Cardiac Troponin I.
Creator
Getfield, Cecile A., Huang, Xupei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description
Restrictive cardiomyopathy (RCM) is represented in part by left ventricular stiffness and diastolic dysfunction. Missense mutations of the cardiac troponin I (cTnI) gene cause idiopathic RCM. These mutations are located in the C-terminus of cTnI and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical patients with RCM have been generated previously and express the mutant cTnI in their hearts. RCM-linked mutations increase cardiac myofilament Ca2+...
Show moreRestrictive cardiomyopathy (RCM) is represented in part by left ventricular stiffness and diastolic dysfunction. Missense mutations of the cardiac troponin I (cTnI) gene cause idiopathic RCM. These mutations are located in the C-terminus of cTnI and affect cardiac relaxation. Transgenic mouse models presenting the pathology observed in clinical patients with RCM have been generated previously and express the mutant cTnI in their hearts. RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity and promote diastolic dysfunction in the heart. Previous studies using double transgenic mice (cTnI/R193H/ND) showed that ventricular relaxation is enhanced in the cTnI/R193H transgenic mice. In this study, another double transgenic mouse model, (cTnI/R193H/ND/KO), provides an avenue to investigate its rescuing effects on RCMlinked mutations in the cTnI /R193H/KO mouse. Use of molecular biological techniques, transgenic animal developments and murine echocardiography in this study has culminated into a greater understanding of RCM and diastolic dysfunction.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00004196, http://purl.flvc.org/fau/fd/FA00004196
Subject Headings
Biochemical markers -- Diagnostic use, Cardiovascular system -- Pathophysiology, Coronary heart disease -- Molecular diagnosis, Mice as laboratory animals, Molecular biology
Format
Document (PDF)