Huntingtin inclusions do not down-regulate specific genes in the R6/2 Huntington's disease mouse.
Huntingtin inclusions do not down-regulate specific genes in the R6/2 Huntington's disease mouse.
复制标题
亨廷顿蛋白内含物不会下调 R6/2 亨廷顿病小鼠中的特定基因。
DOI：
10.1111/j.1460-9568.2006.04871.x
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Cha,J-HJ
中科院分区：
文献类型：
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作者：
Sadri-Vakili,G;Menon,AS;Farrell,LA;Keller-McGandy,CE;Cantuti-Castelvetri,I;Standaert,DG;Augood,SJ;Yohrling,GJ;Cha,J-HJ
转录失调是亨廷顿病（HD）的主要致病机制; HD和HD转基因小鼠模型显示特定基因在mRNA表达水平下调。此外，已在R6/2小鼠和HD患者的脑中鉴定出神经元核内包涵体（NIIs）。一种可能性是NII通过隔离转录因子而导致转录失调。因此，我们使用双标记原位杂交结合免疫组织化学和激光捕获显微切割结合定量真实的时间PCR评估了R6/2小鼠中NII与转录失调之间的关系。NII阳性和NII阴性神经元之间的特定基因的转录水平没有差异。这些结果表明，NII不会引起R6/2纹状体中D2、PPE和PSS mRNA水平的降低，因此不参与该HD模型中这些特定基因的下调。此外，这些观察结果反对NIIs防止HD中转录失调的观点。
Transcriptional dysregulation is a central pathogenic mechanism in Huntington's disease (HD); HD and transgenic mouse models of HD demonstrate down‐regulation of specific genes at the level of mRNA expression. Furthermore, neuronal intranuclear inclusions (NIIs) have been identified in the brains of R6/2 mice and HD patients. One possibility is that NIIs contribute to transcriptional dysregulation by sequestering transcription factors. We therefore assessed the relationship between NIIs and transcriptional dysregulation in the R6/2 mouse, using double‐labelin situhybridization combined with immunohistochemistry, and laser capture microdissection combined with quantitative real‐time PCR. There was no difference in transcript levels of specific genes between NII‐positive and NII‐negative neurons. These results demonstrate that NIIs do not cause decreases in D2, PPE and PSS mRNA levels in R6/2 striatum and therefore are not involved in the down‐regulation of these specific genes in this HD model. In addition, these observations argue against the notion that NIIs protect against transcriptional dysregulation in HD.