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Cardiac Effects of Huntington's Disease in Murine Models
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Cardiac Effects of Huntington's Disease in Murine Models. |
| 개인저자 | Child, Daniel David. |
| 단체저자명 | University of Pennsylvania. Cell and Molecular Biology. |
| 발행사항 | [S.l.]: University of Pennsylvania., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 150 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-02B. Dissertation Abstract International |
| ISBN | 9781085568494 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Advisor: Davidson, Beverly L. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Huntington's disease (HD) is an autosomal dominant disease known for its severe neurologic phenotype. However, the causative protein in HD, mutant huntingtin (mHTT), is widely expressed across tissue types and may have profound consequences for peripheral organs. Notably, heart disease is the second leading cause of death in HD patients, but if or how cardiac mHTT expression causes pathology is still unknown. Here, I characterize the cardiac phenotype in two HD mouse models and show that dysregulated mTORC1 activity is a key underlying mechanism. I show that normal heart growth is limited in HD mouse models, with mass regulated independent of systemic changes. Additionally, cardiac mTORC1 activity is decreased in HD mice starting at a presymptomatic time point in a manner that requires cardiac mHTT expression. The impaired activity results from decreased PI3K/Akt/mTOR signaling at early time points and Rheb mislocalization at later disease stages. As a result of mTORC1 dysregulation, HD mice have increased mortality, inability to hypertrophy, and increased pathologic changes in response to stress. Notably, this phenotype is reversed in HD mice with exogenously activated mTORC1. Thus, I propose that mHTT expression in HD hearts dysregulates mTORC1 and leads to increased mortality with heart disease. |
| 일반주제명 | Cellular biology. Genetics. Medicine. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
