دورية أكاديمية
Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown.
| العنوان: | Effects on murine behavior and lifespan of selectively decreasing expression of mutant huntingtin allele by supt4h knockdown. |
|---|---|
| المؤلفون: | Hui-Min Cheng, Yijuang Chern, I-Hui Chen, Chia-Rung Liu, Sih-Huei Li, Seung J Chun, Frank Rigo, C Frank Bennett, Ning Deng, Yanan Feng, Chyuan-Sheng Lin, Yu-Ting Yan, Stanley N Cohen, Tzu-Hao Cheng |
| المصدر: | PLoS Genetics, Vol 11, Iss 3, p e1005043 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | Genetics, QH426-470 |
| الوصف: | Production of protein containing lengthy stretches of polyglutamine encoded by multiple repeats of the trinucleotide CAG is a hallmark of Huntington's disease (HD) and of a variety of other inherited degenerative neurological and neuromuscular disorders. Earlier work has shown that interference with production of the transcription elongation protein SUPT4H results in decreased cellular capacity to transcribe mutant huntingtin gene (Htt) alleles containing long CAG expansions, but has little effect on expression of genes containing short CAG stretches. zQ175 and R6/2 are genetically engineered mouse strains whose genomes contain human HTT alleles that include greatly expanded CAG repeats and which are used as animal models for HD. Here we show that reduction of SUPT4H expression in brains of zQ175 mice by intracerebroventricular bolus injection of antisense 2'-O-methoxyethyl oligonucleotides (ASOs) directed against Supt4h, or in R6/2 mice by deletion of one copy of the Supt4h gene, results in a decrease in mRNA and protein encoded specifically by mutant Htt alleles. We further show that reduction of SUPT4H in mouse brains is associated with decreased HTT protein aggregation, and in R6/2 mice, also with prolonged lifespan and delay of the motor impairment that normally develops in these animals. Our findings support the view that targeting of SUPT4H function may be useful as a therapeutic countermeasure against HD. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7390 1553-7404 |
| Relation: | http://europepmc.org/articles/PMC4356588?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404 |
| DOI: | 10.1371/journal.pgen.1005043 |
| URL الوصول: | https://doaj.org/article/e7c32a5397ef466e8cb0f5e061e4f8bf |
| رقم الأكسشن: | edsdoj.7c32a5397ef466e8cb0f5e061e4f8bf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537390 15537404 |
|---|---|
| DOI: | 10.1371/journal.pgen.1005043 |