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A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology.

Mar Matarin | Dervis A Salih | Marina Yasvoina | Damian M Cummings | Sebastian Guelfi | Wenfei Liu | Muzammil A Nahaboo Solim | Thomas G Moens | Rocio Moreno Paublete | Shabinah S Ali | Marina Perona | Roshni Desai | Kenneth J Smith | Judy Latcham | Michael Fulleylove | Jill C Richardson | John Hardy | Frances A Edwards
Cell reports | 2015

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. All data are available and searchable at http://www.mouseac.org.

Pubmed ID: 25620700

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Associated grants

  • Agency: Parkinson's UK, United Kingdom
    Id: G-0907
  • Agency: Medical Research Council, United Kingdom
    Id: MR/J011851/1

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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geNORM (tool)

RRID:SCR_006763

Software to determine most stable reference (housekeeping) genes from set of tested candidate reference genes in given sample panel. From this, gene expression normalization factor can be calculated for each sample based geometric mean of user-defined number of reference genes.

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