Neurotoxicity Research

, Volume 17, Issue 4, pp 360–379

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

  • Amee J. George
  • Lavinia Gordon
  • Tim Beissbarth
  • Irene Koukoulas
  • R. M. Damian Holsinger
  • Victoria Perreau
  • Roberto Cappai
  • Seong-Seng Tan
  • Colin L. Masters
  • Hamish S. Scott
  • Qiao-Xin Li
Article

DOI: 10.1007/s12640-009-9112-3

Cite this article as:
George, A.J., Gordon, L., Beissbarth, T. et al. Neurotox Res (2010) 17: 360. doi:10.1007/s12640-009-9112-3

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.

Keywords

Serial analysis of gene expression (SAGE) Alzheimer’s disease Tg2576 Amyloid precursor protein Amyloid-β Transgenic mice 

Abbreviations

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

Supplementary material

12640_2009_9112_MOESM1_ESM.pdf (145 kb)
Fig. S1Schematic of the approach used for the GOStat analysis performed on the Tg2576 and NTg SAGE library data (PDF 145 kb)
12640_2009_9112_MOESM2_ESM.doc (85 kb)
Supplementary Table S1 (DOC 85 kb)
12640_2009_9112_MOESM3_ESM.pdf (4.5 mb)
Table S2Matched SAGE tags (PDF 4621 kb)
12640_2009_9112_MOESM4_ESM.pdf (293 kb)
Table S3Unmatched SAGE tags (PDF 293 kb)
12640_2009_9112_MOESM5_ESM.doc (44 kb)
Supplementary Table S4 (DOC 44 kb)

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Amee J. George
    • 1
    • 5
  • Lavinia Gordon
    • 2
  • Tim Beissbarth
    • 2
  • Irene Koukoulas
    • 3
  • R. M. Damian Holsinger
    • 1
  • Victoria Perreau
    • 1
    • 4
  • Roberto Cappai
    • 1
    • 4
  • Seong-Seng Tan
    • 3
  • Colin L. Masters
    • 1
    • 4
  • Hamish S. Scott
    • 2
  • Qiao-Xin Li
    • 1
    • 4
  1. 1.Department of PathologyThe University of Melbourne and The Mental Health Research Institute of VictoriaParkvilleAustralia
  2. 2.The Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  3. 3.Howard Florey InstituteThe University of MelbourneParkvilleAustralia
  4. 4.Centre for NeuroscienceThe University of MelbourneParkvilleAustralia
  5. 5.Growth Control Laboratory, Research DivisionPeter MacCallum Cancer CentreEast MelbourneAustralia