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Cardiac MTSS1 Downregulation Protects Against Dilated Cardiomyopathy in a Sex-Specific Manner
Cardiac MTSS1 Downregulation Protects Against Dilated Cardiomyopathy in a Sex-Specific Manner
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151112
- ISBN
- 9798382834832
- DDC
- 574
- 서명/저자
- Cardiac MTSS1 Downregulation Protects Against Dilated Cardiomyopathy in a Sex-Specific Manner
- 발행사항
- [Sl] : University of Pennsylvania, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 81 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Musunuru, Kiran;Cappola, Thomas P.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2024.
- 초록/해제
- 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.
- 일반주제명
- Molecular biology
- 일반주제명
- Pathology
- 일반주제명
- Genetics
- 일반주제명
- Sexuality
- 키워드
- Animal models
- 기타저자
- University of Pennsylvania Cell and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■006m o d
■007cr#unu||||||||
■020 ▼a9798382834832
■035 ▼a(MiAaPQ)AAI31144363
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aChoe, Dongwook Christian.
■24510▼aCardiac MTSS1 Downregulation Protects Against Dilated Cardiomyopathy in a Sex-Specific Manner
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a81 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Musunuru, Kiran;Cappola, Thomas P.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2024.
■520 ▼aEnhancer 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.
■590 ▼aSchool code: 0175.
■650 4▼aMolecular biology
■650 4▼aPathology
■650 4▼aGenetics
■650 4▼aSexuality
■653 ▼aDilated cardiomyopathy
■653 ▼aMTSS1 downregulation
■653 ▼aIsoproterenol induction
■653 ▼aAnimal models
■653 ▼aCardioprotective traits
■690 ▼a0307
■690 ▼a0211
■690 ▼a0369
■690 ▼a0571
■71020▼aUniversity of Pennsylvania▼bCell and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160755▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
