Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models
Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in human and affected in disease models
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DOI：
10.1152/physiolgenomics.00125.2007
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发表时间：
2008-04-22
影响因子：
4.6
通讯作者：
de Chaldee, Michel
中科院分区：
文献类型：
--
作者：
Brochier, Camille;Gaillard, Marie-Claude;de Chaldee, Michel
通过基因表达的系列分析，我们收集了成年野生型小鼠大脑 11 个区域的定量转录组数据：眼眶、前边缘、扣带皮层、运动、体感和内嗅皮质、尾壳核、伏核、丘脑、黑质和腹侧被盖区。该数据库对超过 120 万个 cDNA 标签进行了测序，是探索大脑功能和疾病的强大资源。作为说明，我们进行了区域间比较，发现了 315 个差异转录本。其中大多数的特征描述很差，20% 缺乏功能注释。对于 78 个差异转录本，我们通过实时定量 RT-PCR 提供小鼠大脑区域的独立表达水平测量。我们还展示了使用原位杂交来实现基础设施分辨率的示例。接下来，我们通过 30 个转录本证明了区域富集在人脑中是保守的。然后，我们量化了亨廷顿病 R6/2 小鼠模型和帕金森病 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 小鼠模型中区域富集转录物的表达水平，并观察到 R6/2 小鼠纹状体、大脑皮层、丘脑和黑质以及 MPTP 治疗小鼠纹状体的显着变化。这些结果表明，此处提供的小鼠大脑基因表达数据可用于探索病理生理学模型并揭示人脑区域差异表达的转录本。
Using serial analysis of gene expression, we collected quantitative transcriptome data in 11 regions of the adult wild-type mouse brain: the orbital, prelimbic, cingulate, motor, somatosensory, and entorhinal cortices, the caudate-putamen, the nucleus accumbens, the thalamus, the substantia nigra, and the ventral tegmental area. With > 1.2 million cDNA tags sequenced, this database is a powerful resource to explore brain functions and disorders. As an illustration, we performed interregional comparisons and found 315 differential transcripts. Most of them are poorly characterized and 20% lack functional annotation. For 78 differential transcripts, we provide independent expression level measurements in mouse brain regions by real-time quantitative RT-PCR. We also show examples where we used in situ hybridization to achieve infrastructural resolution. For 30 transcripts, we next demonstrated that regional enrichment is conserved in the human brain. We then quantified the expression levels of region-enriched transcripts in the R6/2 mouse model of Huntington disease and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease and observed significant alterations in the striatum, cerebral cortex, thalamus and substantia nigra of R6/2 mice and in the striatum of MPTP-treated mice. These results show that the gene expression data provided here for the mouse brain can be used to explore pathophysiological models and disclose transcripts differentially expressed in human brain regions.