Decreased expression of striatal signaling genes in a mouse model of Huntington's disease
Decreased expression of striatal signaling genes in a mouse model of Huntington's disease
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DOI：
10.1093/hmg/9.9.1259
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发表时间：
2000-05-22
影响因子：
3.5
通讯作者：
Olson, JM
中科院分区：
文献类型：
--
作者：
Luthi-Carter, R;Strand, A;Olson, JM
为了了解人类亨廷顿蛋白中由多聚谷氨酰胺重复扩增介导的基因表达变化，我们使用寡核苷酸DNA阵列对转基因亨廷顿病（HD）模型R6/2小鼠中的6000个纹状体mRNA进行了分析。我们发现在早期和晚期症状时间点（6和12周龄），神经递质、钙和类维生素A信号通路的mRNA编码组分水平降低。我们在另一种HD小鼠模型（N171- 82 Q）中观察到类似的基因表达变化。这些结果表明，突变亨廷顿蛋白直接或间接地减少了一组不同的基因的表达参与已知是至关重要的纹状体神经元功能的信号通路。
To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile similar to 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.