자료유형  

 학위논문

Control Number  

0017160755

International Standard Book Number  

9798382834832

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Choe, Dongwook Christian.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Pennsylvania., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

81 p.

General Note  

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

General Note  

Advisor: Musunuru, Kiran;Cappola, Thomas P.

Dissertation Note  

Thesis (Ph.D.)--University of Pennsylvania, 2024.

Summary, Etc.  

요약Enhancer variants that reduce the expression of MTSS1 in the human left ventricle have been associated with cardioprotective traits in genome-wide association studies. However, the effect of MTSS1 downregulation on the development of heart disease had not been studied in cell or animal models and warranted further investigation. In this study, we evaluated whether cardiac MTSS1 downregulation could be protective against dilated cardiomyopathy. To do this, we 1) assessed the associations of MTSS1 enhancer variants with a variety of cardiac structural and functional traits, as well as phenome-wide traits, in the UK Biobank cohort, both in the general cohort and stratified by sex. We also 2) used a mouse model of dilated cardiomyopathy [Tg(Myh6-Tpm1*D230N)HJcf] to test the effect of heterozygous knockout of the mouse Mtss1 ortholog on cardiac structural and functional traits separately in female mice and male mice. Finally, we 3) knocked out MTSS1 in two induced pluripotent stem cell-cardiomyocyte models of dilated cardiomyopathy [TNNT2 R173W] [TPM1 D230N] and measured their spontaneous beating rate response to isoproterenol induction.In summation, my thesis provides 1) evidence that cardiac MTSS1 downregulation in the female sex protects against dilated cardiomyopathy and 2) evidence that cardiac MTSS1 downregulation in the male sex has no effect against dilated cardiomyopathy.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Pathology.

Subject Added Entry-Topical Term  

Genetics.

Subject Added Entry-Topical Term  

Sexuality.

Index Term-Uncontrolled  

Dilated cardiomyopathy

Index Term-Uncontrolled  

MTSS1 downregulation

Index Term-Uncontrolled  

Isoproterenol induction

Index Term-Uncontrolled  

Animal models

Index Term-Uncontrolled  

Cardioprotective traits

Added Entry-Corporate Name  

University of Pennsylvania Cell and Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 85-12B.

Electronic Location and Access  

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Control Number  

joongbu:657933