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Cell Rep. 2015 Feb 3;10(4):633-44. doi: 10.1016/j.celrep.2014.12.041. Epub 2015 Jan 22.

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

Author information

1
Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London WC1N 3BG, UK; Reta Lila Research Laboratories and Department of Molecular Neuroscience, UCL, Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK.
2
Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK.
3
Reta Lila Research Laboratories and Department of Molecular Neuroscience, UCL, Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK.
4
Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK; Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
5
Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
6
Department of Neuroinflammation, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
7
Department of Laboratory Animal Science, GlaxoSmithKline R&D, Stevenage SG1 2NY, UK.
8
Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage SG1 2NY, UK.
9
Reta Lila Research Laboratories and Department of Molecular Neuroscience, UCL, Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK. Electronic address: j.hardy@ucl.ac.uk.
10
Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, London WC1E 6BT, UK. Electronic address: f.a.edwards@ucl.ac.uk.

Abstract

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.

PMID:
25620700
DOI:
10.1016/j.celrep.2014.12.041
[Indexed for MEDLINE]
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