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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Deng, Yu Bissada, Nagat Hayden, Michael R. Slow, Elizabeth J. Graham, Rona K. Osmand, Alexander P. Devon, Rebecca S. Vaid, Kuljeet Wetzel, Ronald Lu, Ge Pearson, Jacqui Leavitt, Blair R. |
| Description | Author Affiliation: Slow EJ ( Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada V5Z 4H4.); |
| Abstract | We have serendipitously established a mouse that expresses an N-terminal human huntingtin (htt) fragment with an expanded polyglutamine repeat (approximately 120) under the control of the endogenous human promoter (shortstop). Frequent and widespread htt inclusions occur early in shortstop mice. Despite these inclusions, shortstop mice display no clinical evidence of neuronal dysfunction and no neuronal degeneration as determined by brain weight, striatal volume, and striatal neuronal count. These results indicate that htt inclusions are not pathogenic in vivo. In contrast, the full-length yeast artificial chromosome (YAC) 128 model with the identical polyglutamine length and same level of transgenic protein expression as the shortstop demonstrates significant neuronal dysfunction and loss. In contrast to the YAC128 mouse, which demonstrates enhanced susceptibility to excitotoxic death, the shortstop mouse is protected from excitotoxicity, providing in vivo evidence suggesting that neurodegeneration in Huntington disease is mediated by excitotoxic mechanisms. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 32 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Behavioral Symptoms Physiopathology Disease Models, Animal Huntington Disease Pathology Inclusion Bodies Nerve Tissue Proteins Genetics Neurons Nuclear Proteins Analysis Of Variance Animals Brain Chromosomes, Artificial, Yeast Computational Biology DNA Primers Mice Mice, Transgenic Physiology Promoter Regions, Genetic Rotarod Performance Test Sequence Analysis, DNA Comparative Study Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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