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Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression
DC Field | Value | Language |
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dc.contributor.author | Pouladi, Mahmoud A. | - |
dc.contributor.author | Xie, Yuanyun | - |
dc.contributor.author | Skotte, Niels Henning | - |
dc.contributor.author | Ehrnhoefer, Dagmar E. | - |
dc.contributor.author | Kim, Jeong Eun | - |
dc.contributor.author | Yang, X. William | - |
dc.contributor.author | Friedlander, Robert M. | - |
dc.contributor.author | Hayden, Michael R. | - |
dc.contributor.author | Leavitt, Blair R. | - |
dc.contributor.author | Paganetti, Paolo | - |
dc.contributor.author | Bissada, Nagat | - |
dc.contributor.author | Graham, Rona K. | - |
dc.date.accessioned | 2012-06-15T00:50:54Z | - |
dc.date.available | 2012-06-15T00:50:54Z | - |
dc.date.issued | 2010-04-15 | - |
dc.identifier.citation | HUMAN MOLECULAR GENETICS; Vol.19 8; 1528-1538 | ko_KR |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | https://hdl.handle.net/10371/77095 | - |
dc.description.abstract | Levels of full-length huntingtin (FL htt) influence organ and body weight, independent of polyglutamine length. The growth hormone-insulin like growth factor-1 (GH-IGF-1) axis is well established as a regulator of organ growth and body weight. In this study, we investigate the involvement of the IGF-1 pathway in mediating the effect of htt on body weight. IGF-1 expression was examined in transgenic mouse lines expressing different levels of FL wild-type (WT) htt (YAC18 mice), FL mutant htt (YAC128 and BACHD mice) and truncated mutant htt (shortstop mice). We demonstrate that htt influences body weight by modulating the IGF-1 pathway. Plasma IGF-1 levels correlate with body weight and htt levels in the transgenic YAC mice expressing human htt. The effect of htt on IGF-1 expression is independent of CAG size. No effect on body weight is observed in transgenic YAC mice expressing a truncated N-terminal htt fragment (shortstop), indicating that FL htt is required for the modulation of IGF-1 expression. Treatment with 17 beta-estradiol (17 beta-ED) lowers the levels of circulating IGF-1 in mammals. Treatment of YAC128 with 17 beta-ED, but not placebo, reduces plasma IGF-1 levels and decreases the body weight of YAC128 animals to WT levels. Furthermore, given the ubiquitous expression of IGF-1 within the central nervous system, we also examined the impact of FL htt levels on IGF-1 expression in different regions of the brain, including the striatum, cerebellum of YAC18, YAC128 and littermate WT mice. We demonstrate that the levels of FL htt influence IGF-1 expression in striatal tissues. Our data identify a novel function for FL htt in influencing IGF-1 expression. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | OXFORD UNIV PRESS | ko_KR |
dc.title | Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 김정은 | - |
dc.identifier.doi | 10.1093/hmg/ddq026 | - |
dc.citation.journaltitle | HUMAN MOLECULAR GENETICS | - |
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