A Genome-wide Gene-Expression Analysis and Database in Transgenic Mice during Development of Amyloid or Tau Pathology
A Genome-wide Gene-Expression Analysis and Database in Transgenic Mice during Development of Amyloid or Tau Pathology
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DOI：
10.1016/j.celrep.2014.12.041
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发表时间：
2015-02-03
期刊：
影响因子：
8.8
通讯作者：
Edwards, Frances A.
中科院分区：
文献类型：
--
作者：
Matarin, Mar;Salih, Dervis A.;Edwards, Frances A.
我们提供了微阵列数据，比较了四种“淀粉样蛋白”转基因小鼠（突变型人APP、PSEN 1或APP/PSEN 1）和“TAU”转基因小鼠（突变型人MAPT基因）的全基因组差异表达和一生中的病理学。微阵列数据通过qPCR并通过与人类研究（包括全基因组关联研究（GWAS）命中）进行比较来验证。免疫基因表达与斑块密切相关，而突触基因与神经元缠结呈负相关。免疫基因模块的网络分析揭示了淀粉样蛋白小鼠海马中的六个枢纽基因，其中四个与皮质相同。TAU小鼠的海马网络相似，除了Trem 2仅在淀粉样蛋白小鼠中具有枢纽状态。TAU小鼠的皮质网络完全不同，具有更多的枢纽基因，与其他网络的共同点很少，这表明FTDP中皮质功能障碍特异性的原因17。这一资源开辟了许多调查领域。
We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid'' transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU'' transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation.