Morphological Changes Associated with Severe Early Onset Dilated Cardiomyopathy Caused by a Mutation in Alpha Tropomyosin

Persistent Link:
http://hdl.handle.net/10150/579427
Title:
Morphological Changes Associated with Severe Early Onset Dilated Cardiomyopathy Caused by a Mutation in Alpha Tropomyosin
Author:
Harder, Megan Michelle
Issue Date:
2015
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
A point mutation in alpha tropomyosin (Tm) Asp230Asn (D230N) has been found in two unrelated multigenerational families to be causative for dilated cardiomyopathy (DCM). In these families, a distinct "bimodal" distribution of severity was observed whereby children have a severe DCM and adults have a mild to moderate phenotype. If children harboring this mutation survive the initial presentation of DCM, they often regain some systolic function. This "bimodal" presentation led us to ask what changes occur in the heart between fetal and postnatal life that could account for this; a potential candidate was the switch from fetal to adult cardiac troponin T (cTnT). Therefore, we hypothesize that temporal isoform switching by cTnT results in the "bimodal" phenotype observed in patients with D230N. Whole hearts, obtained from transgenic littermates of a murine model showed overall enlargement of the ventricles. H&E staining showed normal fiber size, distribution and no evidence of inflammation indicating that there is no myocarditis. Additionally, there was no histopathological evidence of collagen deposition in trichrome stained hearts. These results suggest a primary DCM in which the D230N mutation causes a structural DCM that is worsened in the presence of fetal TnT possibly due to further alterations in structure.
Type:
text; Electronic Thesis
Degree Name:
B.S.H.S.
Degree Level:
bachelors
Degree Program:
Honors College; Physiology
Degree Grantor:
University of Arizona
Advisor:
Tardiff, Jil

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleMorphological Changes Associated with Severe Early Onset Dilated Cardiomyopathy Caused by a Mutation in Alpha Tropomyosinen_US
dc.contributor.authorHarder, Megan Michelleen
dc.date.issued2015en
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractA point mutation in alpha tropomyosin (Tm) Asp230Asn (D230N) has been found in two unrelated multigenerational families to be causative for dilated cardiomyopathy (DCM). In these families, a distinct "bimodal" distribution of severity was observed whereby children have a severe DCM and adults have a mild to moderate phenotype. If children harboring this mutation survive the initial presentation of DCM, they often regain some systolic function. This "bimodal" presentation led us to ask what changes occur in the heart between fetal and postnatal life that could account for this; a potential candidate was the switch from fetal to adult cardiac troponin T (cTnT). Therefore, we hypothesize that temporal isoform switching by cTnT results in the "bimodal" phenotype observed in patients with D230N. Whole hearts, obtained from transgenic littermates of a murine model showed overall enlargement of the ventricles. H&E staining showed normal fiber size, distribution and no evidence of inflammation indicating that there is no myocarditis. Additionally, there was no histopathological evidence of collagen deposition in trichrome stained hearts. These results suggest a primary DCM in which the D230N mutation causes a structural DCM that is worsened in the presence of fetal TnT possibly due to further alterations in structure.en
dc.typetexten
dc.typeElectronic Thesisen
thesis.degree.nameB.S.H.S.en
thesis.degree.levelbachelorsen
thesis.degree.disciplineHonors Collegeen
thesis.degree.disciplinePhysiologyen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorTardiff, Jilen
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