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A Serial Analysis of Gene Expression Profile of the Alzheimer’s Disease Tg2576 Mouse Model

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Abstract

Serial analysis of gene expression (SAGE), a technique that allows for the simultaneous detection of expression levels of the entire genome without a priori knowledge of gene sequences, was used to examine the transcriptional expression pattern of the Tg2576 mouse model of Alzheimer’s disease (AD). Pairwise comparison between the Tg2576 and nontransgenic SAGE libraries identified a number of differentially expressed genes in the Tg2576 SAGE library, some of which were not previously revealed by the microarray studies. Real-time PCR was used to validate a panel of genes selected from the SAGE analysis in the Tg2576 mouse brain, as well as the hippocampus and temporal cortex of sporadic AD and normal age-matched controls. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 5 (NDUFA5) and FXYD domain-containing ion transport regulator 6 (FXYD6) were found to be significantly decreased in the Tg2576 mouse brain and AD hippocampus. PTEN-induced putative kinase 1 (PINK1), phosphatidylethanolamine binding protein (PEBP), crystalline μ (CRYM), and neurogranin (NRGN) were significantly decreased in AD tissues. The gene ontologies represented in the Tg2576 data were statistically analyzed and demonstrated a significant under-representation of genes involved with G-protein-coupled receptor signaling and odorant binding, while genes significantly over-represented were focused on cellular communication and cellular physiological processes. The novel approach of profiling the Tg2576 mouse brain using SAGE has identified different genes that could subsequently be examined for their potential as peripheral diagnostic and prognostic markers for Alzheimer’s disease.

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Abbreviations

Aβ:

Amyloid-beta

AD:

Alzheimer’s disease

APP:

Amyloid protein precursor

APPsw:

APP with the Swedish mutation

EST:

Expressed sequence tag

f :

Frequency

GO:

Gene ontology

MGI:

Mouse Genome Informatics

NTg:

Nontransgenic

PMI:

Postmortem interval

SAGE:

Serial analysis of gene expression

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Acknowledgments

This work was supported in part by grants from the National Health and Medical Research Council of Australia #208978 (AG, RH, RC, QXL, CM). AG was a recipient of Alzheimer’s Australia Research travel grant. Funding for the UCI-ADRC was provided by NIH/NIA grant P50 AG16573. We would also like to thank Karen Hsiao-Ashe for the Tg2576 mice.

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Author notes

  1. Amee J. George

    Present address: Growth Control Laboratory, Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia

Authors and Affiliations

  1. Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Parkville, VIC, 3052, Australia

    Amee J. George, R. M. Damian Holsinger, Victoria Perreau, Roberto Cappai, Colin L. Masters & Qiao-Xin Li

  2. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia

    Lavinia Gordon, Tim Beissbarth & Hamish S. Scott

  3. Howard Florey Institute, The University of Melbourne, Parkville, VIC, 3010, Australia

    Irene Koukoulas & Seong-Seng Tan

  4. Centre for Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia

    Victoria Perreau, Roberto Cappai, Colin L. Masters & Qiao-Xin Li

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Corresponding author

Correspondence to Qiao-Xin Li.

Additional information

Hamish S. Scott and Qiao-Xin Li equally share senior co-authorship.

Electronic supplementary material

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Fig. S1

Schematic of the approach used for the GOStat analysis performed on the Tg2576 and NTg SAGE library data (PDF 145 kb)

Supplementary Table S1 (DOC 85 kb)

Table S2

Matched SAGE tags (PDF 4621 kb)

Table S3

Unmatched SAGE tags (PDF 293 kb)

Supplementary Table S4 (DOC 44 kb)

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George, A.J., Gordon, L., Beissbarth, T. et al. A Serial Analysis of Gene Expression Profile of the Alzheimer’s Disease Tg2576 Mouse Model. Neurotox Res 17, 360–379 (2010). https://doi.org/10.1007/s12640-009-9112-3

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  • DOI: https://doi.org/10.1007/s12640-009-9112-3

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