Expression profiling of the solute carrier gene family in the mouse brain.

Expression profiling of the solute carrier gene family in the mouse brain.
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DOI:
10.1124/jpet.108.149831
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发表时间:
2009-05
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
--
通讯作者:
Wang J
Wang J
中科院分区:
其他
文献类型:
--
作者:
Dahlin A;Royall J;Hohmann JG;Wang J

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溶质载体(SLC)超家族是存在于哺乳动物细胞中的一类主要的膜转运蛋白。虽然SLC转运蛋白在中枢神经系统中发挥着重要而多样的作用,但绝大多数SLC基因在哺乳动物脑中的定位和功能在很大程度上是未知的。利用Allen Brain Atlas的高通量原位杂交数据,我们系统地、定量地分析了307个SLC基因在成年C57BL/6J小鼠脑中的空间分布和细胞分布,这些基因占目前已知的小鼠SLC基因的近90%。我们的分析表明,307个SLC基因中有252个(82%)存在于大脑中,其中很大一部分基因处于低到中等表达水平。对20个大脑解剖分区的评估显示,SLC基因的复杂性水平相当,但在转录丰富方面存在显著差异。表达的SLC基因分布多样,从几乎无处不在到高度定位。20个脑区的功能注释,包括血-脑和血-脑脊液(CSF)屏障,表明SLC转运体在支持大脑能量利用、神经传递、营养供应和脑脊液产生方面发挥重要作用。此外,等级聚类分析揭示了与神经解剖组织相关的错综复杂的SLC表达模式。我们的研究还揭示了SLC基因存在于明确的脑微结构中,并描述了可能表达单个SLC基因的细胞类型。这些结果为研究者探索SLC基因在神经生理和病理过程中的作用提供了有用的资源。
The solute carrier (Slc) superfamily is a major group of membrane transport proteins present in mammalian cells. While Slc transporters play essential and diverse roles in the central nervous system, the localization and function of the vast majority of Slc genes in the mammalian brain are largely unknown. Using high throughput in situ hybridization data generated by the Allen Brain Atlas, we systematically and quantitatively analyzed the spatial and cellular distribution of 307 Slc genes, which represent nearly 90% of presently known mouse Slc genes, in the adult C57BL/6J mouse brain. Our analysis showed that 252 (82%) of the 307 Slc genes are present in the brain, and a large proportion of these genes were detected at low to moderate expression levels. Evaluation of 20 anatomical brain subdivisions demonstrated a comparable level of Slc gene complexity, but significant difference in transcript enrichment. The distribution of the expressed Slc genes was diverse, ranging from near-ubiquitous to highly localized. Functional annotation in 20 brain regions, including the blood-brain and blood-cerebral spinal fluid (CSF) barriers, suggest major roles of Slc transporters in supporting brain energy utilization, neurotransmission, nutrient supply, and CSF production. Further, hierarchical cluster analysis revealed intricate Slc expression patterns associated with neuroanatomical organization. Our studies also revealed Slc genes present within defined brain microstructures and described the putative cell types expressing individual Slc genes. These results provide a useful resource for investigators to explore the roles of Slc genes in neurophysiological and pathological processes.
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