Divergent and nonuniform gene expression patterns in mouse brain
Divergent and nonuniform gene expression patterns in mouse brain
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DOI：
10.1073/pnas.1003732107
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发表时间：
2010-11-02
影响因子：
11.1
通讯作者：
Jones, Allan R.
中科院分区：
文献类型：
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作者：
Morris, John A.;Royall, Joshua J.;Jones, Allan R.
在理解与表型相关的基因序列和表达水平的变化方面已经取得了相当大的进展，但遗传多样性如何转化为复杂的表型差异仍然知之甚少。在这里，我们研究了遗传背景和基因表达的空间模式之间的关系在7个品系的小鼠，提供了最广泛的细胞分辨率的比较分析的基因表达在哺乳动物大脑中的日期。使用全面的全脑解剖覆盖范围（超过200个脑区），我们应用原位杂交技术分析了49个编码知名药物靶标的基因的空间表达模式。值得注意的是，超过50%的基因检测显示菌株间表达变异。此外，变异性在应变和神经解剖区域之间分布不均匀，表明了某些组织原则。首先，菌株之间的表达差异程度反映了系谱关系。第二，表达模式的差异集中在更高级的大脑区域，如皮层和海马。大脑中基因表达模式的差异可能会显著影响实验室小鼠品系对神经活性药物的行为和反应，并可能有助于解释人类对神经活性药物反应的个体差异。
Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brain-wide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs.