| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000434099 |
| 005 | | 20200226140839 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781085568494 |
| 035 | |
▼a (MiAaPQ)AAI13814526 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 610 |
| 100 | 1 |
▼a Child, Daniel David. |
| 245 | 10 |
▼a Cardiac Effects of Huntington's Disease in Murine Models. |
| 260 | |
▼a [S.l.]:
▼b University of Pennsylvania.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 150 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-02, Section: B. |
| 500 | |
▼a Advisor: Davidson, Beverly L. |
| 502 | 1 |
▼a Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a 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. |
| 590 | |
▼a School code: 0175. |
| 650 | 4 |
▼a Cellular biology. |
| 650 | 4 |
▼a Genetics. |
| 650 | 4 |
▼a Medicine. |
| 690 | |
▼a 0379 |
| 690 | |
▼a 0369 |
| 690 | |
▼a 0564 |
| 710 | 20 |
▼a University of Pennsylvania.
▼b Cell and Molecular Biology. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-02B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0175 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15490793
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1816162 |
| 991 | |
▼a E-BOOK |